Podcasts about tcrs

Welcome to another episode of the VJ Oncology Podcast, where we bring you the forefront of cancer research and clinical... The post Expanding Cell Therapy – TILs, TCRs & CARs in Lung Cancer and Melanoma appeared first on VJOncology.

Dr. Thierry Mora and Dr. Aleksandra Walczak co-lead the Statistical biophysics group within Laboratoire de physique de l'ENS (LPENS) at the Ecole normale supérieure (Paris, France). Physicists by training, Dr. Mora and Dr. Walczak entered the field of the analysis of the immune system in a time when the first AIRR-seq datasets were becoming available. They have applied biophysics, neuroscience, and information theory perspectives to understand V(D)J recombination and quantify diversity. The group has published many software tools for the analysis of immune repertoires, including IGoR (to infer V(D)J recombination related processes from sequencing data), Sonia (infer selection pressures on features of amino acid CDR3 sequences), ALICE (detect TCR involved in immune responses from single RepSeq datasets), and PUBLIC (for analyzing sharing of TCRs, and predict public clones). In this episode of On AIRR, Dr. Mora and Dr. Walczak discuss the relevance and challenges of quantifying diversity and the questions that remain unanswered. They think of immune repertoire diversity in the same way as one could think of English language sentences, and try to learn the grammar of the combinations and quantify it. They also provide an overview of some of the software tools developed by their group. Comments are welcome to the inbox of onairr@airr-community.org  or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast.   The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding. Announcements and links Statistical biophysics @ ENS. The website of the group. https://sites.google.com/view/statbiophysens/home Tools mentioned: IGoR: https://github.com/statbiophys/IGoR Sonia: https://github.com/statbiophys/SONIA SoNNia: https://github.com/statbiophys/sonnia ALICE: https://github.com/pogorely/ALICE PUBLIC: https://github.com/yuvalel/PUBLIC

Over the past few weeks, I've been on a transformative journey—a personal creative retreat that has pushed me to reflect, adjust, and ultimately break through the resistance that was holding me back. If you've ever felt stuck, uninspired, or like your creative energy just isn't flowing the way you know it could, this episode is for you. In this episode, I share what this retreat has been like, how I've learned to embrace the power of solitude, and the surprising lessons I've discovered about adjusting expectations and going with the flow. You'll hear about the exact moment my creative flow state kicked in and how journaling, reflection, and even unexpected obstacles became stepping stones to greater clarity and purpose. In this episode, I'll walk you through: How I overcame resistance and unlocked a new level of creative energy. What I've learned about the importance of setting aside time for personal retreats. Practical takeaways on how you can create your own space for reflection, even if it's just for a couple of hours or a weekend. The habits, tools, and strategies I've refined to support this flow state moving forward. My hope is that by the end of this episode, you'll feel inspired to break out of the routines that might be holding you back and to intentionally create space for your own breakthroughs. Whether you've done personal retreats before or this is a new concept, I believe this episode will spark ideas and motivation for your next steps. Call to Action: If this episode inspires you to create your own personal retreat, I'd love to hear from you. Email me at cliff@cliffravenscraft.com and share when, where, and how long you plan to make it happen. And if you're already in the habit of doing personal retreats, I'd love to hear about your experiences—feel free to attach a photo if you'd like! Also, if you're on an entrepreneurial journey and want to explore working together in one of my mastermind groups or through coaching, email me to let me know. Let's connect!

In Episode 35 of Init Talks, host Lyubov Ozeretskovskaya (@LoveFortySix) welcomes Emma Galasso (@bullissemma), a rising figure in the sim racing world and a dynamic professional in the automotive industry. With a background in film and her current role as a Brand Partnerships Coordinator, Emma brings a unique perspective to the intersection of creativity, racing, and business. She shares insights into her career journey, her passion for motorsport, and how these two worlds blend to fuel her ambitions. Emma's sim racing story is as inspiring as it is impressive. She races every Monday in her Assetto Corsa league, competing in diverse cars like Indy Lights and TCRs on tracks around the globe. As a top 30 qualifier in the 2022 Porsche Esports Series and top 20 qualifier in 2023 on Gran Turismo 7, Emma has demonstrated her skill and determination. This year, she achieved a remarkable P7 in the Ferrari Esports Challenge ACC Americas Qualifier and placed 2nd in the women's category of the USEF.GG Qualifiers on ACC. Despite starting her sim racing journey with no experience and finishing last just three years ago, Emma's current personal best is a 6th place finish. Her next goal: winning a race in her league and proving that success in sim racing is a journey, not an overnight accomplishment. Looking ahead, Emma's journey with Init Talks will continue in a new capacity as she joins the show as a host starting in 2025, alternating with Lyubov. Tune in to this episode to hear Emma's fascinating story, her reflections on perseverance in sim racing, and her plans to inspire and empower others in the community through her future role as a host. So buckle up – Screen to Speed starts now! ===== (Oo---x---oO) ===== 00:00:00 Introduction to Screen to Speed 00:00:55 Meet Emma Galasso: Sim Racer and Brand Partnership Coordinator 00:01:28 Emma's Journey into Sim Racing 00:03:12 Sim Racing Setup and Evolution 00:05:46 Challenges and Learning in Sim Racing 00:08:16 Practice Routine and Coaching 00:10:32 Sim Racing Community and League Details 00:12:29 Highlights and Achievements in Sim Racing 00:14:31 Real-Life Racing Experiences 00:17:12 Professional Journey in the Automotive Industry 00:24:52 Comparing Motorsports in Europe and the US 00:31:30 The Appeal of IMSA and Daytona 500 00:32:18 Sim Racing vs. Real Life Racing 00:33:30 The Challenges and Rewards of Sim Racing 00:36:36 Balancing Aggression and Strategy in Racing 00:43:01 Encouraging Women in Sim Racing 00:53:05 Future Goals and Advice for New Sim Racers 01:00:02 Conclusion and Final Thoughts ==================== The Motoring Podcast Network : Years of racing, wrenching and Motorsports experience brings together a top notch collection of knowledge, stories and information. #everyonehasastory #gtmbreakfix - motoringpodcast.net More Information: https://www.motoringpodcast.net/ Become a VIP at: https://www.patreon.com/ Online Magazine: https://www.gtmotorsports.org/ INIT eSports focuses on sim racing events and digital tournaments. They bring eSports content to fans and sponsorship opportunities to brands, while maximizing audience reach across multiple sports, industries, and platforms. INIT eSports is a woman-led company where Diversity, Equity, Inclusion and Accessibility is in their DNA, and their platform aims to combat bullying and cheating to help make the eSports world as safe and fair as possible. To learn more, be sure to logon to www.initesports.gg today or follow them on social media @initesports, join their discord, check out their YouTube Channel, or follow their live content via Twitch. Copyright INIT eSports. This content originally aired on the INIT Talks livestreams via Twitch. This episode is part of the Motoring Podcast Network and has been republished with permission.

Teller cash recyclers are a modern day necessity in bank branches. Due to the large amount of cash banks handle, they need a reliable method to count it that doesn't rely on bankers manually counting it by hand. Teller cash recyclers automate both counting and sorting for cash. However, newer cash recyclers are also arriving on the market, with improved cassette technology, security features and more. What's on the horizon for TCRs? This was the topic of today's episode of the Bank Customer Experience Podcast, sponsored by Cook Solutions Group.Bradley Cooper, editor of ATM Marketplace, spoke with Scott Fieber, chief strategy officer at Cook Solutions Group Ryan Loebs, TCR expert about the history of TCRs and trends to look for in the near future.Topics covered included:Costs of newer TCRs.How to plan to replace older units.Why we are seeing a resurgence in TCRs.How to measure ROI.You can listen to the podcast in its entirety below.

We're in Munich

Auftakt zum Transcontinental Race Special: Heute besprechen Straps und Flo die letzten Vorbereitungen vor dem Start ins 4000 Kilometer lange Rennen quer durch Europa.Christoph Strasser geht nach zwei Siegen bei den letzten TCRs als Titelverteidiger in die zehnte Auflage des Ultracycling Klassikers und hat dementsprechend große Ziele. Die Besetzung war so hochkarätig wie noch nie, die Konkurrenz sehr stark, und die Motivation dementsprechend groß.Doch bereits bei der Anreise lief es nicht ganz rund. Was für treue Gäste der deutschen Bahn wahrscheinlich eine ganz normale Zugfahrt ist, war für Straps eine kleine Odyssee. Kaputter Zug, Umsteigen in einen bereits vollen Zug, am Boden kauern statt Schlafwagen, kein Platz für das Rad – es hat ein bisschen Kraft gekostet. Aber nachdem ihn sein S-Works Roubaix von Brüssel nach Roubaix gebracht hat, lief es richtig gut: Die Packtaschen ordnen und neu befüllen, die ersten Kilometer der Strecke im Training abfahren und die Leute treffen, die das Rennen organisieren und daran teilnehmen. Das Flair war nicht nur in den berühmten Duschen des Velodroms besonders.Doch kurz vor dem Start begannen technische Probleme mit dem Navigationsgerät. Ein letztes Update und die finale Synchronisation der geplanten Route über exakt 3.983 km und 41.100 Höhenmeter wollte einfach nicht klappen. Irgendwie war die Route dann doch auf den Garmin geladen, aber ein mulmiges Gefühl blieb.Nach einer Runde im legendären Velodrom und einer neutralisierten Phase ging es los! Über 300 Teilnehmer und Teilnehmerinnen machten sich auf den Weg nach Istanbul. Zuerst noch auf einem Parcours mit offroad Passagen und Pflastersteinen, bevor ab Geraardsbergen die selbst geplanten Routen das Starterfeld wie einen Schwarm Hummeln über Belgien ausschwärmen ließen. Fever-Tree Gewinnspiel:Gewinne ein „Fever-Tree Cocktail Package“ mit je500ml Fever-Tree Mojito Mixer, Margarita Mixer, Passionfruit Martini Mixer; dazu 1x Mixer-Guide und 1x Baumwolltasche.Die Drinks sind übrigens bei vinospirit.aterhältlich: www.vinospirit.at/Inspirationen/World-of-Fever-TreeGewinnfrage: Wieviele Höhenmeter (umgerechnet in Plesch) hat die geplante Route von Straps beim TCRNo10? Hinweis: Wer die erste Folge zum TCRNo10 gehört hat, wird die Umrechnung schaffen.Sende bis 31.8.2024 um 23:59 Uhr die richtige Antwort an: sitzfleisch [ at ] christophstrasser.at

BUFFALO, NY- August 8, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on August 5, 2024, entitled, “Chemical complementarity of tumor resident, T-cell receptor CDR3s and renalase-1 correlates with increased melanoma survival.” As mentioned in the Abstract of this study, overexpression of the secretory protein renalase-1 negatively impacts the survival of melanoma and pancreatic cancer patients, while inhibition of renalase-1 signaling drives tumor rejection by promoting T-cell activation. Thus, researchers Saif Zaman, Fred S. Gorelick, Andrea Chrobrutskiy, Boris I. Chobrutskiy, Gary V. Desir, and George Blanck from Yale School of Medicine, Veteran's Administration Healthcare System, Oregon Health and Science University Hospital, Morsani College of Medicine, and H. Lee Moffitt Cancer Center and Research Institute, investigated the chemical complementarity between melanoma-resident, T-cell receptor (TCR) complementarity-determining region 3 (CDR3) amino acid sequences (AAs) and the renalase-1 protein. “In this study, we asked whether the RNLS protein could potentially be a tumor antigen by examining chemical complementarity between melanoma tumor-resident TCR CDR3s and the AA sequence of RNLS.” The results suggest that there could be biologically relevant antigenic interaction between RNLS epitopes and T-cell receptors (TCRs). “We hypothesize that RNLS protein could be recognized by TCRs, leading to local immune responses against melanoma, similar to what we have previously demonstrated with wildtype cancer antigens in the melanoma and glioblastoma settings.” DOI - https://doi.org/10.18632/oncotarget.28633 Correspondence to - George Blanck - gblanck@usf.edu Video short - https://www.youtube.com/watch?v=p3X9IgPQFJw Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28633 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, RNLS, melanoma, T-cell receptor CDR3s, chemical complementarity About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Join us as we chat with a multifamily real estate expert who has spent 2 decades in property management operations and now thrives on the supplier side. Her passion for changing the space through innovation and her dedication to customer experience sets her apart in the industry.We discuss how she brings operational expertise to sales, focusing on making the customer interaction enjoyable and efficient. Learn about her journey of taking a leap of faith into the supplier side, the crucial role of technology, and why she believes in the power of one-on-one connections.Tune in for invaluable tips for Regional and Property managers, and discover her insights on overcoming fear and making bold decisions that drive success.Marysa has a passion for multi-family real estate and changing the space through ingenuity and innovation. Marysa spent 19 years in property management operations with TCRS, Riverstone Residential Group and Greystar, with her last role of Senior Director of Operations and Business Development. She was elated to have the unique opportunity in bringing her operational background and expertise to the Entrata Sales team and has been overseeing strategic teams with a focus on supporting larger fee managers & multifamily ownership partners with long term innovation planning and technology strategies.Marysa is also an engaged industry advocate and has held many leadership positions in industry associations including local, state and national apartment associations as well as local city and municipal tasks forces focused on attainable housing.LinkedIn: http://www.linkedin.com/in/marysaraymondCompany: http://www.entrata.comHear from Marysa about: The intimidating leap of faith she took and why.Her passion for innovating and advancing the industry.The focused time she spends with her team.The inner critic that spoke every time she was promoted.Her love for the industry and how everyone is willing to help. The operations role she believes is the most challenging.The importance of transparency with ownership. Her great advice and reminder on not letting fear drive your decisions.Connect with us!LinkedIn: https://www.linkedin.com/in/lesliemathisStreamline Website: https://www.streamlinemultifamily.comEmpowHER Website: https://empowhermultifamily.comInstagram: https://www.instagram.com/empowhermultifamily https://www.instagram.com/streamlinemultifamilySubscribe and leave a review for the Multifamily Streamlined Podcast here.Streamline Multifamily Group is your specialized consulting partner for multifamily operations, training, and more! We offer consultative support in project management, construction, development, renovations, auditing, and also organize industry events. Remember, no matter how well your property is doing, it could be doing better. Contact Leslie at LMathis@StreamlineMultifamily.com for more information. 

Dr. Diwakar Davar and Dr. Jason Luke discuss key abstracts from the 2024 ASCO Annual Meeting that explore triplet therapy in advanced melanoma, TIL cell therapy in immune checkpoint inhibitor–naive patients, and other novel approaches that could shape the future of immunotherapy in melanoma and beyond.  TRANSCRIPT Dr. Diwakar Davar: Hello and welcome to the ASCO Daily News Podcast. I am your guest host, Dr. Diwakar Davar. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. I'm delighted to have my friend and colleague, Dr. Jason Luke, on the podcast today to discuss key abstracts in melanoma and immunotherapy that will be featured and highlighted at the 2024 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the director of the Cancer Immunotherapeutic Center, as well as the associate director for clinical research at the University of Pittsburgh's Hillman Cancer Center.  You will find our full disclosures in the transcript of this episode.  Jason, as always, it's a pleasure to have you on this podcast to hear your key insights on trials in the immunotherapy space and melanoma development paradigm, and to have you back on this podcast to highlight some of this work.  Dr. Jason Luke: Thanks so much for the opportunity to participate. I always enjoy this heading into ASCO.  Dr. Diwakar Davar: We're going to go ahead and talk about three abstracts in the melanoma space, and we will be starting with Abstract 9504. Abstract 9504 essentially is the RELATIVITY-048 study. It describes the efficacy and safety of the triplet nivolumab, relatlimab, and ipilimumab regimen in advanced PD-1 naive melanoma. So in this abstract highlighted by Dr. Ascierto and colleagues, they report on the results of this phase 2 trial in this setting. By way of background, PD-1 inhibitors and immune checkpoint inhibitors starting in PD-1 and CTLA-4, as well as PD-1 and LAG-3, are all FDA-approved on the basis of several pivotal phase 3 trials, including KEYNOTE-006, CheckMate-066, CheckMate-067, and most recently, RELATIVITY-047. Jason, can you briefly summarize for this audience what we know about each of these drugs, at least the two combinations that we have at this time?  Dr. Jason Luke: For sure. And of course, these anti PD-1 agents, became a backbone in oncology and in melanoma dating back to more than 10 years ago now, that response rates in the treatment-naive setting to anti PD-1 with either pembrolizumab or nivolumab are roughly in the range of mid-30s to high-40s. And we've seen clinical trials adding on second agents. You alluded to them with the seminal study being CheckMate-067, where we combined a PD-1 antibody and CTLA-4 antibody or nivo + ipi. And there the response rate was increased to approximately 56%. And more recently, we have data combining PD-1 inhibitors with anti-LAG-3. So that's nivolumab and relatlimab. Now, in that trial, RELATIVITY-047, the overall response rate was described as 43%. And so that sounds, on a first pass, like a lower number, of course, than what we heard for nivolumab and ipilimumab. We have to be cautious, however, that the cross-trial comparison between those studies is somewhat fraught due to different patient populations and different study design. So I think most of us think that the response rate or the long-term outcomes between PD-1, CTLA-4, and PD-1 LAG-3 are probably roughly similar, albeit that, of course, we have much better or much longer follow up for the nivo + ipi combo.  The one other caveat to this, of course then, is that the side effect profile of these two combinations is distinct, where the incidence of high-grade immune-related adverse events is going to be roughly half with nivolumab and relatlimab, a combination of what you would see with the nivolumab and ipilimumab. So that has caused a lot of us to try to think about where we would use these different combinations. But we do see that all of these treatments can land a durable long-term response in the subset of patients that do have an initial treatment benefit. The landmark, I think, for the field has been the 7-and-a-half-year median overall survival that we've seen with PD-1 plus CTLA-4, nivo + ipi; of course, we don't have such long-term follow up for PD-1 and LAG-3. But I think that's the setting for thinking about the rationale for combining a triplet regimen of PD-1, CTLA-4, and LAG-3. Dr. Diwakar Davar: So, Jason, in your mind, given the difference in the disparity and durability of the responses for the 067 regimen of nivo-ipi, and the RELATIVITY-047 regiment of nivo-rela, what is the standard of care in the U.S., and how does it change in the rest of the world, knowing that nivo-rela is not necessarily approved in all jurisdictions? Dr. Jason Luke: So this is a major complication in our field, is that there is perhaps not complete agreement across the world in terms of what the frontline standard of care should be. I think most United States investigators, or those of us that really treat melanoma most of the time, would suggest that a combination regimen, given the enhanced response rate and longer-term outcomes, should be the consideration for the majority of patients. In fact, in my practice, it's hard to think of who I would treat with a monotherapy PD-1 approach in the PD-1 naive setting. So either nivo + ipi or nivo + rela. As you alluded to however, in other regulatory settings throughout the world, combinations might not actually even be approved at this point. So PD-1 monotherapy would be the backbone of that setting. It does set up some complications when you think about a comparator arm; say you were going to look at various combinations, probably PD-1 monotherapy would be the worldwide comparator. You have to understand though, in the United States, I think that that's a less attractive option. Dr. Diwakar Davar: So in RELATIVITY-047, Dr. Ascierto and his colleagues are looking at generating a triplet. And in this case, they looked at this in the context of frontline metastatic melanoma, 46 patients. Very interestingly, the dose of ipilimumab studied here was 1 mg/kg through 8 weeks, not the 3 mg/kg every three weeks times four doses using 067, or even the low dose ipilimumab regimen that you studied in the second line setting, which was 1 mg/kg every 3 weeks for 4 doses. So let's talk about the results and specifically the implications of potentially studying lower doses of ipi. Dr. Jason Luke: I appreciate you raising that point. I think it's really important as we think about this dataset because this triplet regimen is not by any means the only version of a triplet that could be developed using these agents. So just to give the high-level numbers from the abstract, we see from these data that the overall response rate is described as 59% and 78%, a disease control rate with patients having an unreached link. So duration of response of unreached, and then the progression-free survival at about 5 months. So those are really interesting data. But as was alluded to, it's not totally clear to me that that's the best that we could do with this regimen.   Now, you alluded to this low-dose ipilimumab schedule at 1 mg/kg every 8 weeks, and it's really important to note that we have no benchmark for that regimen in melanoma oncology. And in fact, the one study that used that regimen, which was the adjuvant study of nivolumab and ipilimumab, known as CheckMate915, is in fact the only immune checkpoint inhibitor study in melanoma oncology that was actually negative. That study noted no benefit to adding ipilimumab at 1 mg/kg every 8 weeks on top of nivolumab, again, the adjuvant setting. So it's a little bit curious to then understand what it means in this study to have that amount of ipilimumab added to the rela-nivo backbone. And that manifests in a few different ways. We see the response rate here at 59%. Again, if you compare that just against the standard nivo + ipi dosing schedule, it's about the same. So is that really an advantage to having the triplet as compared to just doing standard nivo + ipi?   We do see that it manifests in a slightly lower rate of grade 3/4 immune-related adverse events, at 39%. That's a little bit lower than what we'd expect for standard nivo + ipi. But again, I think that that emphasizes to me the possibility that some efficacy was left on the table by using this very low dose ipilimumab regimen. I think that's really a concern. It's not clear to me that these triplet data really differentiate from what we'd expect with the already approved regimen of nivo + ipi. Therefore, it makes it difficult to think about how would we really want to move this regimen forward, or should there be more work done about dose and schedule to optimize how we might want to do this?  Dr. Diwakar Davar: As far as triplet therapy in the context of frontline metastatic melanoma, meaning triplet immune therapy, because there are at least several targeted therapy triplets that are FDA-approved, [but] not necessarily widely utilized. How would you summarize the future for triplet therapy? Do you think it's potentially attractive? Do you think it's very attractive with some caveats? Dr. Jason Luke: Well, I think it's attractive, and we have 3 independently active agents. And so I do think it's a priority for the field to try to figure out how we could optimize the therapy. We've had such a revolution in melanoma oncology, talking about 7.5-year median survival from CheckMate-067, but that still implies that 7.5 years, half the patients have passed away. There's more to do here. And so I do think it should be a priority to sort this out. I guess I would be cautious, though, about advancing this regimen directly to a phase 3 trial because it doesn't seem clear to me that this is optimized in terms of what the outcome could be. If we're willing to tolerate higher rates of toxicity from other dose schedules of nivo-ipi alone, then I think we should do a little bit more here to potentially explore the space that might be possible to increase that overall response rate a little more without getting into a completely exaggerated toxicity profile that would be unacceptable. So, I do think it's exciting, but there's possibly more to do before really think about going big time with this. Dr. Diwakar Davar: Great. So now we'll switch gears and move from frontline metastatic melanoma to the second line and beyond looking at a new agent and contextualizing the effects of that actually in the frontline settings. So Abstract 9505 describes the efficacy and safety of lifileucel, which is essentially autologous tumor-infiltrating lymphocyte cell therapies, also known as TIL, in combination with pembrolizumab in patients with ICI naive, so not necessarily pretreated, but ICI naive metastatic or unresectable melanoma. This is data from the IOV-COM-202 Cohort 1A oral abstract presented by Dr. Thomas and colleagues. In this abstract, Dr. Thomas and colleagues are presenting data from the 1A cohort, which is the phase 2 portion of the frontline trial that is evaluating autologous TIL with pembro in checkpoint inhibited naive metastatic melanoma.  By way of background, TIL is FDA approved on the basis of several cohorts from a phase 2 trial. The data has been presented multiple times now by Drs. Sarli, Chesney, and multiple colleagues of ours. And essentially autologous TIL, which is generated from a surgical procedure in which a patient undergoes a surgery to extract a tumor from which T cells are then grown after ex vivo expansion and rapid expansion protocol. The entire procedure was essentially pioneered by several colleagues at the NCI, primarily Dr. Steve Rosenberg, and this approach produces objective response rates of approximately 31% to 36%. And the most recent publication demonstrated that at median follow up of approximately 2 years, the median duration of response was not reached. The median OS was about 14 months and PFS was about 4 months or so. So, can you contextualize the results of the abstract in the frontline setting? And then we'll talk a little bit about where we think this is going to go. Dr. Jason Luke: So I think this is a timely study given the recent approval. And in the abstract presented here, we see an early data cut from the PD-1 naive study, as you alluded to. So here we had 22 patients and distributed across various states of advanced melanoma. Ten out of the 22 had M1C, but there also were smatterings of earlier M1A and M1B at 18.2% and 9.1%. So this is important, as we think who the treatment population is that's going to be optimized with a TIL procedure. The median sum of diameters, meaning how much tumor burden the patients have, was about 5.5cm, and I'll note that that's a relatively modest amount of tumor burden, albeit not that unusual for an early-stage trial. So of the patients that participated, 8 had BRAF mutations so that's 36%. That's not that high, but it's reasonable. And I think the important overlying number, the response rate so far in the study, with about 17 months of follow up, was 63.6%, and that includes 22% or 23% having complete response. So those are interesting data.  And another point that was made in the abstract, which we've all seen, is that responses to TIL, all of immunotherapy but especially TIL, do seem to mature over time, meaning they deepen over time. So it's possible the response rate could go up some extent as we watch this study advance. So I think these are exciting data on some level. Also, a 63.6% response rate sounds pretty impressive, but we do have to put that in the context of a double checkpoint blockade, which we just got done discussing, gives you almost a 60% response rate, 59% response rate. So then the question really is: Is it worth the amount of effort that we could go into generating a TIL product in a treatment naive patient, and put them through the lymphodepletion that is associated with TIL and the high dose interleukin 2 treatment that accompanies the reinfusion of the TIL, if you're going to get a response rate that's roughly the same as what you would get if you gave them off the shelf nivo plus ipilimumab?  At this point it's a little bit hard to know the answer to that question. I think it could be possible that the answer is yes, because we don't know exactly which populations or patients are most likely to benefit from each of these therapies. And if it could be teased out who's not going to benefit to nivo + ipi from the get-go, then of course, we would want to offer them a therapy that has that frontline potential, durable, long-term response. But I have to say, on a one-to-one with TIL therapy, you get a lot of toxicity initially with the treatment; with nivo + ipi on the back end, you get a fair amount of toxicity with the treatment. How are we going to judge those two things? And I think we probably need a larger dataset to really have a good handle on that.  So these are interesting early data, but it's not totally clear to me that even if this holds up all the way through the trial, and we're going to talk about the design of the registration trial here in a second, a 60% response rate on its own without further biomarker stratification is a little bit hard for me to see in clinical practice why we would want to do that, given we can already just go off the shelf and give checkpoint inhibitors. Dr. Diwakar Davar: So that brings us to TILVANCE-301. So TILVANCE is a phase 3 trial. It's a registration intent trial by our Iovance colleagues evaluating the pembro-TIL regimen versus pembrolizumab alone. So in this phase 3 trial, approximately 670 patients will be randomized to either arm A, which is lifileucel + pembro. And in this arm A, patients are going to be getting lifileucel with the tumor resection, non-myeloablative lymphoid depletion, the lifileucel and abbreviated course of high-dose IL-2, and thereafter, continued pembro for the study mandated duration versus arm B, where patients will be getting just pembrolizumab monotherapy per label. Arm B patients, per the design, may cross over to receive TIL monotherapy at the time of central-blinded, radiology-confirmed disease progression.   The study design otherwise is fairly routine and, per most of our registration trials these days, patients have actually been permitted to receive neoadjuvant and adjuvant therapy, including checkpoint inhibitors, as long as the receipt of the therapy was more than 6 months prior to the inclusion of the patient in that registration trial. The dual primary efficacy endpoints as stated are BICR-assessed objective response rate as well as PFS, and the key secondary endpoint is overall survival.   So Jason, what are your thoughts on the study design and potentially the regulatory implications, particularly given, one, the control arm of pembro monotherapy, and two, the role of TIL crossover to receive TIL monotherapy at the time of BICR mandated progression for arm B? Dr. Jason Luke: So this goes to a few points that we've touched on already in the discussion here. When we think about the primary endpoints for this study, with one of them being overall response rate, one has to assume that that's a given that they would get that. I feel like that's a low bar. And we go back to that cross-trial comparison. If their results end up being that the response rates are about 60%, I don't know that that differentiates necessarily from what's already available in the field with combination immune checkpoint blockade. For the purposes of the study that would mean it's a positive study, so I think that would probably be good. But again, the comparator to pembrolizumab monotherapy, I think some of us would argue, isn't really consistent with what we would do with a patient in our clinic. So it's not that it's bad per se, but I think there's going to be a whole lot of cross-trial comparison. So if the study is positive, that would be good for getting the drug available. It's still a bit hard though, based on the preliminary data that I've seen, to imagine how this would have uptake in terms of utilization as a frontline therapy.  You alluded to the crossover, and I think there, the assumption is that patients who get TIL therapy as a second line perhaps would have an attenuated benefit. But I'm not sure that's really true. It certainly looks from the data that we have, like the patients who benefit most from TIL are going to be those who didn't respond to anti PD-1 in the front line. So I'm not sure how much difference there's going to be between first- and second-line TIL therapy, but those data will kind of wait to be seen. So I think it's an important study. Of course, the accelerated approval of TIL as a later line therapy is dependent on this trial being positive. So there is some risk that if this trial ended up not being positive, that that could have regulatory implications on the utility or availability of TILs, a subsequent line therapy. But all of these, I guess we'll have to wait to see the results. We do hope for a positive trial here, although I think it'll be nuanced to sort of interpret those data given that pembrolizumab monotherapy control arm.  Dr. Diwakar Davar: Fantastic. So we've learned a lot about TIL, both its use in the second-line setting and this very exciting but potentially risky frontline trial that is ongoing at some centers in the United States and certainly a lot of ex-U.S. enrollment.   So we'll now pivot to a related product which actually belongs to a much larger class of agents that are antigen specific T-cell therapies in a variety of different formats. And that is Abstract 9507, which is the “Phase 1 safety and efficacy of IMC-F106C, a PRAME × CD3 ImmTAC bispecific, in post-checkpoint cutaneous melanoma (CM).” Now, in this abstract, Dr. Omid Hamid and colleagues reported the results of this phase 1 trial. As a disclosure, I'm an investigator and the last author on this manuscript. Jason, it would be important for our audience, for us to maybe firstly, outline the PRAME as a target, and then the ImmTAC as a platform prior to discussing these results. So let's start with the target PRAME, which I think is a target that you know well. So why don't you start with the target and we'll talk a little bit about that and then the platform? Dr. Jason Luke: Yeah, so I think for the audience, being aware of PRAME, or the Preferentially Expressed Antigen in Melanoma, is going to be quite important moving into the future. So PRAME as a therapeutic target is a cancer testis antigen that's overexpressed in tumor tissues. And of course the name has melanoma in it, but it's not uniquely present in melanoma. So the expression patterns of PRAME as a target are very high in melanoma. So in cutaneous disease, this is upwards of almost 100%, somewhere between 95% and 100%, in metastatic melanoma tissues. And PRAME has several different roles on a molecular level, although I don't think for our purposes here, it's so much important to be aware of them, but rather that this is a very highly expressed target, which then can make it attractive for using T cell receptor-based therapies. And so in the case we're talking about here on the ImmTAC platform, that's a CD3 PRAME×CD3 bispecific approach. But of course there are other approaches that can also be taken, such as TCR T cells that directly go after PRAME itself. Dr. Diwakar Davar: Let's now talk about the platform and how it differs from some of the other antigen targeting platforms that you have just alluded to. I think the Immtac platform is basically a fusion protein comprising engineered TCRs with a CD3 specific short chain variable fragment. And then the engineered TCR therefore binds antigens in an HLA dependent fashion. But you know quite a lot about some of these alternative platforms, and I think it'll be important to contextualize for the audience the difference between ImmTAC, which is a prototype drug that is already approved in the context of tebentafusp. But how does this differ from some of the other more nuanced platforms, such as the Immatics TCR or TCR platform and TScan TCRT nanoplasmonic platform.  Dr. Jason Luke: Right. So the ImmTAC platform as alluded to is already approved on the market with tebentafusp, which is the gp100-CD3 bispecific molecule. And the advantage of that approach is infusion off the shelf of a drug. The downside of it is that it is a weekly dosing strategy as it stands now. And there are some complicated disease kinetics associated with treatment response, which we'll come back to in the context of the PRAME bispecific. Those are, in contrast with T-cell receptor-transduced T cells, as an alternative strategy, which is a form of adopted cell transfer. So we just got done talking about TIL therapy, which of course, is trying to take lymphocytes out of the tumor and grow them up and then give them back. Here with TCR-transduced T cells, we're talking about taking leukopak from the blood and then using different transfection approaches to try to insert into the lymphocytes of the patient a T cell receptor that recognizes to a certain cancer antigen, in this case, PRAME.  So you alluded to a couple of different companies that have different platforms to do this. Immatics has a molecule called IMA 203, for which there have been data disclosed in the past year, again showing some very interesting responses in patients who have highly refractory melanoma. That process, though, again, does require lymphodepletion before you reinfuse the cells. Again, in contrast, the ImmTAC, which is an off the shelf revenue administer, there you have to make the product and then bring the patient back, lymphodeplete, and give the cells back. Immatics platform uses a viral transfection vector. The T scan approach that you alluded to before uses an approach of a mixed system on multiple HLA backgrounds to try to get past HLA-A*02:01 only, and in this case, uses a plasmid-based transfection syndrome that perhaps can be more broadly utilized given the lack of a lentiviral vector.   So this is a complicated area of technology that starts to get into immune engineering, and I think for the purposes of this discussion, we don't want to belabor it. But both of these technologies, talking about the CD3 bispecific with the off the shelf aspect of it and the adoptive cell transfer, each of these using a T cell receptor-based therapy to try to go after PRAME, I think have very high upsides, and I think we'll initially see it in melanoma over the next year or so. But this is likely to be relevant to multiple tumor types beyond melanoma.  Dr. Diwakar Davar: So let's discuss the results of this phase 1 trial. IMC-F106C, like all other ImmTAC, is administered intravenously and does require step-up dosing. You alluded to the fact that the tebentafusp was approved, and it's one of those drugs that is fortunately otherwise administered weekly, which can be difficult for the patient and requires at least the patient spend the first 3 doses overnight under some kind of monitoring, whether it's in the hospital or extended outpatient monitoring, for at least 23 hours. The efficacy of this agent and this platform appears to be surprising in that you tend to see a relatively low RECIST response rate. We'll have you comment a little bit on why that is the case and what may be the role of ctDNA, as opposed to conventional RECIST in assessing response.   At least in this trial, they mandated pre-testing, but did not require it for study enrollment. And pre-positivity was defined using immunohistochemistry with a relatively low H-score of 1%. And the molecular response definition was a 0.5 log or a 68% ctDNA reduction just prior to the first imaging assessment. So how do you contextualize the results? But maybe before you talk a little bit about the results, the ctDNA aspect, that was a recent publication by Drs. Rich Carvajal, Alex Shoushtari, and I think you are also involved in that.  Dr. Jason Luke: So, I think an interesting observation around tebentafusp has been that ctDNA may be a better predictor of long-term outcomes. And how you define ctDNA response is still something that the field is grappling with, albeit that I think is going to be an important consideration as we think about these novel therapies, these ImmTACs and other CD3 engagers moving into the future. But for the purposes of the abstract here, we see that in the population of patients treated, there were 46 patients with cutaneous melanoma. The majority got monotherapy with IMC-F106C, and that's the PRAME bispecific. So 40 patients that got monotherapy and six who got a combination with checkpoint inhibitor. All these patients had prior treatment with immunotherapy, and most of them had PD-1 and CTLA-4 antibody with a small spanner that also had BRAF inhibitors.  In terms of that PRAME testing that you alluded to, based on the immunohistochemistry H-score greater than 1%, 35 out of 40 patients were positive, so they defined 5 as negative. And we could come back if we have time, but there are other ways to do PRAME testing as well that I think may become unique for different agents, maybe an important biomarker. In the data, 31 out of the 46 patients were RECIST evaluable. The outcomes of those patients were to note that the response rate was 13%, which was four partial responses. But 35% of patients had tumor regression with a disease control rate at 65%. It was clear that there was an enrichment by PRAME positivity for both progression free and overall survival. So those patients who had obvious positivity essentially had a doubling of the PFS and more than the doubling of the OS, 2.1 to 4.1 months for TFS and landmark OS, 40% to 94%. So I think these are quite intriguing data.  It does suggest that for the vast majority of patients, we do see some induction of the antitumor effect, albeit that RECIST might undercall the effect. And so this may become another area where the ctDNA monitoring might be able to help us to understand who is likely to have really long-term benefit from this therapy. And given the number of emerging treatments that we have for melanoma, we might be able to really focus in on that group of patients in terms of optimizing how we would use this drug moving into the future. Dr. Diwakar Davar: So you talked about a response rate, and at first glance, this response rate is a little underwhelming. We're talking about 4 out of 31 RECIST evaluable patients, 13%. So it's in the double digits, but barely. So how enthusiastic are you about the results? How does it contrast with at least the publicly known data from other brain targeting approaches, such as the IMA203 agent, understanding that while they may be all targeting somewhat the same target, they are actually extraordinarily different platforms. One's off the shelf, one's highly customized. How do you contextualize the results? How would it contrast with other cellular approaches?  Dr. Jason Luke: I think it's important, again, to emphasize the point you made, which is that they're very different kinds of treatments. So even though they both target PRAME, they're going to be differently useful, and they could be quite useful for different groups of patients. And so here we see that there is a subfraction of patients who are deriving long-term benefit. And we commonly have an argument in our field about, is overall response rate really a useful monitor that describes a patient-centric outcome? While, of course, patients like to know their tumors are shrinking, what they want the most is for the tumors not to get worse and for them not to pass away from cancer. So I think I'm enthusiastic about these results, but emphasizing the point that we need to better understand who is going to benefit the most from this CD3 bispecific PRAME approach and how we're going to be able to harness that into long term benefit for patients because there's no doubt that an off the shelf therapy has a high degree of value relative to adoptive cell transfer, which sort of requires a big wind up.   So when you say, what does it contrast with? Well, the data for IMA203 has shown more than a 50% response rate in patients with more than 5 lines of therapy for metastatic disease. That really looks quite exciting. And several of those patients are now out for quite an extended period, meaning 2 years or more given only a single dose of IMA203. But again, the caveat being, you have to make the cell product for the patient, and that takes time. You lymphodeplete the patient, not all patients can tolerate that in the refractory disease setting, and then they have to be able to tolerate the reinfusion of the cells. And so this drug, IMC-F106C, looks very promising. Moving into the earlier phase trial that we'll talk about, I think the TCR T cell program has a lot of upsides for patients, especially with refractory disease. And so I think these two different approaches are really on parallel tracks. They both target PRAME, but I don't think they necessarily need to be compared one to one, as if they're going to go head-to-head with each other. Dr. Diwakar Davar: So now we'll talk a little bit about the frontline setting, because on the basis of some of these results, Immunocore is now exploring IMC-F106C frontline melanoma. This trial is actually being presented as a trial in progress at this meeting by Georgina Long and colleagues. Some of us are co-authors in that abstract. And in this study, HLA-A*02:01 positive patients with advanced unresectable melanoma will be randomized one to one to the combination of IMC-F106C, which actually, I think after this meeting will be known as bre-ni in combination with nivolumab versus nivolumab regimens, which will either be nivo or nivo-rela, investigators choice and likely dependent on region. So what do you think of the challenge of this trial? We talked about some of the challenges of the TILVANCE trial earlier. But what is going to be the challenge of this trial and in this setting, particularly given the response rates that we've seen so far? Dr. Jason Luke: Yeah, so, similar to comments we had before, thinking about what the optimal control arm is for a study like this is difficult, and so that'll be important as we think about interpreting the results. One has to assume for the purpose of this conversation that it is a positive trial, and that adding the PRAME bispecific theory does lead to an improvement in progression free survival relative to those in checkpoint alone approaches. And I think the magnitude of that difference is going to be of some relevance. And then I think importantly, also figure out who needs this treatment and who's going to benefit long term are going to be really important considerations.  We alluded to how this drug requires an intensive dosing period at the get go, and so telling patients that they need to come in weekly or bi-weekly initially for some number of weeks before they switch to a longer-term intermittent regimen, that comes with real world considerations for patients, their families, their finances, etc. So the benefit has to be clearly obvious that makes it worthwhile doing that, again, because a default could be giving drugs that we've had for 10 years with the nivolumab and ipilimumab. So there's going to be a lot of cross-trial comparison that is going to necessarily have to take place here to think about what these results really mean in the context of other available therapies.  I think the study is reasonable to do. I think this is a very active agent. There's no doubt there's a subset of patients who seem to benefit a lot from it. And I would just emphasize the point that that's probably going to be the most important thing to really drill down on is under the assumption there's a positive trial, we need to know who those people are so we could optimize giving this kind of a treatment to them. Dr. Diwakar Davar: I guess one important point to underscore what Jason said about potential predictive biomarkers, I think as part of the presentation, Dr. Hamid and colleagues will be talking about a candidate predictive biomarker of this agent, which is potentially class specific and not necessarily agent specific of a T cell signature that potentially could define patients who are more likely to benefit from this agent.  So, Jason, as always, thank you for sharing your expertise and insights with the team today. We certainly look forward to catching up again for our wrap up episode after the annual meeting where we'll talk about some of the data that we could not talk about, particularly the late breaking abstracts and other key advances that will shape the future of, certainly the field of immunotherapy and melanoma, potentially the field of cancer immunotherapy at large. Dr. Jason Luke: Oh, thanks very much for the opportunity. Dr. Diwakar Davar: And thank you to our listeners today. You'll find the links to the abstracts discussed today in the transcript of this episode. And finally, if you value the insights that you hear on this podcast, please take a moment to rate, review, and subscribe wherever you get your podcast. So thank you, and we'll see you soon.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Follow today's speakers:   Dr. Diwakar Davar   @diwakardavar   Dr. Jason Luke   @jasonlukemd      Follow ASCO on social media:    @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn      Disclosures:       Dr. Diwakar Davar:     Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences    Consulting or Advisory Role: Instil Bio, Vedanta Biosciences    Consulting or Advisory Role (Immediate family member): Shionogi    Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences    Research Funding (Inst.): Zucero Therapeutics    Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy       Dr. Jason Luke:    Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX    Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine    Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure    Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)    Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio      

Researchers have developed an artificial intelligence (AI) model, called TRTpred, that can accurately predict tumor-killing immune cells. The AI model was trained using gene-expression profiles from 235 T cell receptors (TCRs) of patients with metastatic melanoma. The model was able to accurately identify tumor-reactive T cells with a 90% accuracy rate. The researchers further refined the selection process by applying algorithms to identify T cells with high binding strength to tumor antigens. The combination of TRTpred and the algorithmic filters, known as MixTRTpred, was validated in mice by identifying tumor-reactive T cells capable of eliminating tumors. The researchers believe this AI model has the potential to revolutionize cancer immunotherapies by offering personalized targeting of the most effective tumor-killing T cells. --- Send in a voice message: https://podcasters.spotify.com/pod/show/tonyphoang/message

Tom and DJ have a great time reliving the excitement of Toms racing TCRs at DaytonaWrite in your emails at Podcast@lizardbrain.lifeJoin the live recording of the podcast on Discord by clicking the link below!This is the link! Click meeeeeeeShow your lizard brains on the outside with Merch!CLICK HERE FOR THE MERCHYoutube Link

O Podcast Volta Rápida chega com a grande notícia da sexta-feira, a renovação de Logan Sargeant com a Williams. Com isso, o que pode ser de Felipe Drugovich na F1? Saiba também todos os detalhes das últimas etapas do TCR South America e TCR Brasil.

Heute blicken wir noch einmal auf das Transcontinental Race zurück, Flo und Straps besprechen die Unterschiede zwischen Ultra Rennen mit Crew und unsupported races, bereiten die Leistungswerte anschaulich auf, rechnen den Kalorienbedarf der 8d:16h:30min in Zimtschnecken um und beantworten eure Fragen, die ihr uns in den letzten Wochen geschickt habt.Außerdem werden die Kosten für ein TCR aufgeschlüsselt, da es immer wieder die Kritik gibt, dass dieses Rennen zu teuer ist. Wieviel kostet das mit Registrierung, Unterkünften und Verpflegung in Summe also wirklich? Und was ist vergleichsweise für einen Ironman, ein RAAM oder den Ötztaler Radmarathon zu investieren?Beim Blick auf die Resultate fällt auf, dass in den Race Reports des TCR und den finalen Finisher Zeiten im GPS Tracking unterschiedliche Infos zu den schnellsten Frauen zu finden sind – und das führt uns zur Frage, warum es eigentlich „nur“ eine Gesamtwertung gibt? Ob das wirklich ein Zeichen von Gleichstellung und Wertschätzung ist, können wir hier nicht klären sondern nur unsere persönlichen Meinungen dazu abgeben. Das ist vielleicht ein Thema für eine eigene Folge.Ein kleiner Auszug der Fragen, die heute beantwortet werden: Mechanische Schaltung statt Di2? Routenplanung, Organisation der GPX Files, Heatmap Interpretation, Garmin Edge?Schlafentzug, Pausenmanagement, Koffein Wirkung?Durchfall, Verstopfung, Ernährung und Magen-Darm-Gesundheit?Überschuhe, nasse Füsse, Reserve Socken?Ist Ultracycling eine Sucht, stimmt es, dass viele Leute nicht mehr davon loskommen?Wir lassen die Folge mit einem Mitschnitt der Finisher Party ausklingen und hören den Race Director bei seiner Ansprache, wo er viele Geschichten erzählt, die auf der Strecke passiert sind:Jesko wird für seine großartigen Insta Updates gewürdigt, Patrick hatte den absurdesten Defekt (Schlauchwechsel – Laufrad rollte bergab – Kassette verloren – ewig nicht gefunden- Freilauf defekt – 7 Stunden ins Radgeschäft gegangen usw…), Jaimi Wilson die derbste Sprache die den Podcast Produzenten vor Herausforderungen stellte, Thomas Jacquelinet die krasseste Route, David die originellste Reparatur seines Reifens (Tubeless mit Gartenschlauch repariert), Marei die wildeste Begegnung mit Wildtieren, und Mikko wird geehrt, weil er bisher bei allen TCRs gefinished hat. Ein sehr unterhaltsames Finale unserer #TCRNo9 Sitzfleisch Staffel!

Exclusive - JP Drake's OnlyFans plans! Discover how JP Drake went from collecting trolleys at his family's supermarket to becoming a successful businessman and motorsports enthusiast, all while staying true to himself and breaking barriers for women in racing. John-Paul Drake, Director of Drakes Supermarkets and aspiring Red Bull Commercial Athlete joins the show. JP Drake shares his journey from go-kart racer to successful director of Drake Supermarkets. Discover his family's retail legacy, his passion for customer service, and the flexibility achieved through hard work. Explore topics like work ethics, family time, female representation in motorsport, and the diverse uses of subscription platforms. Gain insights into the Women's World Championship in MotoGP and JP's love for racing. Don't miss this enthralling conversation merging business achievements with a deep devotion to motorsport. For more thrilling discussions spanning Formula 1, V8 Supercars, MotoGP, NASCAR, and the exciting world of go-karting subscribe to Negative Camber, the Motorsport Show negativecamber.co, YouTube or wherever you listen to podcasts.   Chapter Summaries(0:00:00) - Conversations With JP DrakeWe chat about Lisa Pernoudi, Ant Senna, three gigs, my singing, wokeness, passion, and saying what everyone is thinking. (0:11:50) - Family Business and Sliding DoorsWe reflect on hard work, share my job experience at Drake's and Coles, and discuss my Dad's 'sliding doors moment' of starting his own business. (0:18:37) - Life Lessons From a Successful BusinessmanWe discuss family business, nightfill shifts, schoolies week, DJing, and fathers' sacrifices. (0:26:31) - Go Karting, Business Meetings, and OnlyFansWe discuss motorsport opportunities for men and women, Jamie Chadwick and Renee Gracie's successes, Only Fans and our perspectives on the platform. (0:32:17) - Women and Motorsport Subscription MysteryWe examine the lack of female representation in Formula One, the barriers women face in motor racing, and the successes of female drivers. (0:41:26) - Youth Motorsport Budget ChallengesOceane and Iliana's success in the Ferrari club, Ben Hennock's sons' pursuit of the Ferrari driver academy, the competitive nature of motorsport, and budgeting for motorsport are discussed. (0:51:56) - Motorsport and Unique Car DesignMotorsport journey, safety, driving race cars, flying, unique colour scheme inspired by cartoons and Batman. (1:04:33) - Australian Prototype Series and Future PlansBen's love of motorsport, virtual reality workouts, Zagami, Bot Ass, Stephanie Hansen, and the prototype series are discussed. (1:15:05) - Challenges Facing Australian Motorsport CategoriesWe explore the challenges of motorsport in Australia, TCRs, streaming, junior drivers, and the need for categories to work together. (1:25:36) - Passion for Prototype RacingMotorsport's cost, community, prepping, competitive nature, and Super Traforay Asian series at the Bend are discussed. (1:31:59) - Driver Coaching and Race TracksWe discussed racing at Bathurst, Radical cars, smooth tracks, my first time, and Garnett Patterson's skill. (1:44:30) - The High-Stakes Racing WorldSebastian Escondari Miranda's success, disparity between engines, rules for driver academies, and Laila's story of breaking the mold to get on the grid are discussed. (1:49:54) - Women in Formula OneWe discuss steps to F1, Women's Formula Academy, Robert Kubica, McLaren, Oscar Piastri, and Drive to Survive. (1:58:37) - Motorsport DiscussionWe discussed British Touring Series, TCR, Formula One prize money, Dean Canto, Mercedes, Valtteri Bottas, V8 Supercars prize money, and social media presence. (2:09:52) - Motorsport Discussion and MemoriesWe discuss early rallying, Kyle Larson and Scott McLaughlin's Formula One potential, Formula 2 and 3, female drivers, and Go Karting talent. (2:14:37) - Meeting My Wife in Subaru JacketWe discussed motorsport's importance, cost, sponsorships, and the journey to Formula One success.See omnystudio.com/listener for privacy information.

Stress is a natural response to a trigger or a difficult situation. However, not managing stress, by taking care of ourselves, or practicing “self-care”, can lead to issues with our mental and physical health. For instance, 44% of people who are not managing stress report often feeling anxious and depressed, according to a survey by Transamerica Institute (1)(1) “23rd Annual Transamerica Retirement Survey,” nonprofit Transamerica Center for Retirement Studies (TCRS), 2022. TCRS is an operating division of Transamerica InstituteSee omnystudio.com/listener for privacy information.

Managing stress is essential for maintaining good physical, mental, and emotional health. However, fewer than half (41%) of people reported that they are managing their stress on a consistent basis, according to a survey by Transamerica Institute (1). (1) “23rd Annual Transamerica Retirement Survey,” nonprofit Transamerica Center for Retirement Studies (TCRS), 2022. TCRS is an operating division of Transamerica Institute.See omnystudio.com/listener for privacy information.

In our conversation with Wyatt McDonnell, the Co-Founder and CEO of Infinimmune, we discuss his journey to 10X Genomics, his work there, and the founding of Infinimmune. Wyatt is a world-class inventor & immunologist working across a wide range of projects at 10X from launching BEAM (barcode-enabled antigen mapping), working on the Immune Profiling v2 product, and developing various immune repertoire technologies. After making a significant impact on 10X, Wyatt along with 4 other colleagues that had worked together founded Infinimmune to transform human antibodies into drugs. A key theme of the conversation is that tool users greatly outnumber tool builders. This creates an opportunity for the latter to build applications before others. Infinimmune is hiring across business, engineering, and biology roles. And is a home for tool builders. Please get in touch via founders@infinimmune.com if you're interested in applying your expertise to the next generation of antibody therapeutics. Wyatt got his first exposure to science from a Breaking Bad consultant that showed him a redox reaction. To Wyatt, it was like “watching alchemy unfold.” He went to Hillsdale, a small college in Michigan where the largest science class had 60 people. This intimacy played a key role in Wyatt's development and allowed him to speed up his education. He thrived in organic chemistry as a freshman and worked with Frank Steiner, taking 4 of his classes and working in his lab where Wyatt caught the research bug. He had been thinking about medical school but decided to go to Vanderbilt for a PhD program focusing on immunology & precision genomics. While in graduate school, Wyatt saw 10X Genomics' Chromium products taking off. People were coming back to use their instruments, something that is pretty rare in scientific research. This motivated him to apply to 10X and end up joining them to build solutions on top of Chromium. Coming on board in the summer of 2019, the first 90 days were spent figuring things out. Wyatt worked on a wide range of projects, and a key reason was his immunology expertise. He had a strong knowledgebase on TCRs, which was pretty rare at 10X at the time, allowing Wyatt to work across divisions. For example, he got to work with David Jaffe, a co-founder of Infinimmune, on the Enclone project. For Wyatt, working at a market leader like 10X was the perfect example to follow when he built his own startup.After leaving 10X Genomics in the summer of 2022, Wyatt started Infinimmune with people he had worked with at 10X. The company is built with a strong conviction around 3 pillars: We still don't understand immunology that well Adoption of immunology tools has been too slow The best antibodies come from humans The platform is centered on analyzing healthy & disease samples to uncover rare, human antibodies. This requires deep analytical expertise, at the raw sequence read level, to maximize the value from sequencing samples. Infinimmume is building the toolkit to discover effective antibodies from patients that might have survived cancer or have protective genes against Alzheimer's. On this point, for Wyatt, “platforms are only as good as the assets they produce.” Wyatt and the founding team are setting the foundation of the company right now to scale up partnerships and drug development over the next 2 years. Excited to get the update from Wyatt then.

Links:Check out TCRS's websiteTCRS Shrimp SummitCheck out our website!: https://www.globalseafood.org/podcastFollow us on social media!Twitter | Facebook | LinkedIn | InstagramShare your sustainability tips with us podcast@globalseafood.org!If you want to be more involved in the work that we do, become a member of the Global Seafood Alliance: https://www.globalseafood.org/membership/

Among a growing cluster of Pittsburgh biotechs, you'll find BlueSphere Bio, an early-stage company discovering T-cell receptors to leverage against tumor-specific antigens in individual cancer patients. Its leader, CEO Keir Loiacono, Esq., works with a sense of urgency inspired by his own cancer journey. Business of Biotech host Matt Pillar and guest co-host Jon O'Connell, executive editor at Bioprocess Online, toured Bluesphere's state-of-the-art facility perched on the bank of the Monongahela River. Then, we sat down with Loiacono to learn his story and discuss the company's vision for the future of personalized, adoptive cell therapy.Subscribe to the NEW #BusinessofBiotech newsletter at bioprocessonline.com/bob for more real, honest, transparent interactions with the leaders of emerging biotech. It's a once-per-month dose of insight and intel that you'll actually look forward to receiving! Check it out at bioprocessonline.com/bob!

THE biggest week in motorsport ends with a chat with two of the rising stars of the game. We're joined by Porsche Sprint Challenge ace Tom Sargent, fresh from his first taste of a Supercar with DJR and from a winning weekend in the Porsche's at Sydney Motorsport Park. Then there's TCR superstar, Josh Buchan. He's been one of the star performers this year and tells his very unique racing story that has a very different beginning to many of his contemporaries. After that it's business as usual as we digest the massive weekend of Monaco, Indy and Charlotte, plus all the SpeedSeries Hot's and Not's from Sydney. Big show!

THE biggest week in motorsport ends with a chat with two of the rising stars of the game. We're joined by Porsche Sprint Challenge ace Tom Sargent, fresh from his first taste of a Supercar with DJR and from a winning weekend in the Porsche's at Sydney Motorsport Park. Then there's TCR superstar, Josh Buchan. He's been one of the star performers this year and tells his very unique racing story that has a very different beginning to many of his contemporaries. After that it's business as usual as we digest the massive weekend of Monaco, Indy and Charlotte, plus all the SpeedSeries Hot's and Not's from Sydney. Big show!

This month on Episode 36 of Discover CircRes, host Cynthia St. Hilaire highlights original research articles featured in the April 29 and May 13 issues of Circulation Research. This episode also features a conversation with Dr Patricia Nguyen and Jessica D'Addabbo from Stanford University about their study, Human Coronary Plaque T-cells are Clonal and Cross-React to Virus and Self.   Article highlights:   Zanoli, et al. COVID-19 and Vascular Aging   Wang, et al. JP2NT Gene Therapy in a Mouse Heart Failure Mode   Harraz, et al. Piezo1 Is a Mechanosensor in CNS Capillaries   Zhao, et al. BAT sEVs in Exercise Cardioprotection   Cindy St. Hilaire:        Hi, and welcome to Discover CircRes, the podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cyndy St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh. And today, I'll be highlighting the articles from our April 29th and May 13th issues of Circulation Research. I also will speak with Dr Patricia Nguyen and Jessica D'Addabbo from Stanford University about their study, Human Coronary Plaque T-cells are Clonal and Cross-React to Virus and Self.   Cindy St. Hilaire:        The first article I want to share is titled Vascular Dysfunction of COVID 19 Is Partially Reverted in the Long-Term. The first author is Agostino Gaudio and the corresponding author is Luca Zanoli. And they're from the University of Catania. Cardiovascular complications, such as endothelial dysfunction, arterial stiffness, thrombosis and heart disease are common in COVID 19. But how quickly such issues resolve, once the acute phase of the illness has passed, remains unclear. To find out, this group examined aortic and brachial pulse wave velocity, and other measures of arterial stiffness in 90 people who, several months earlier, had been hospitalized with COVID 19. These measurements were compared with data from 180 controls, matched for age, sex, ethnicity and body mass index, whose arterial stiffness had been assessed prior to the pandemic. 41 of the COVID patients were also examined 27 weeks later to assess any changes in arterial stiffness over time. Together, the data showed arterial stiffness was higher in COVID patients than in controls. And though it improved over time, it tended to remain higher than normal for almost a year after COVID.   Cindy St. Hilaire:        This finding could suggest residual structural damage to the arterial walls or possibly, persistent low-grade inflammation in COVID patients. Either way, since arterial stiffness is a predictor of cardiovascular health, its potential longterm effects in COVID patients deserves further longitudinal studies.   Cindy St. Hilaire:        The second article I want to share is titled Gene Therapy with the N-Terminus of Junctophilin-2 Improves Heart Failure in Mice. The first author is Jinxi Wang and the corresponding author is Long-Sheng Song from the University of Iowa. Junctophilin-2 is a protein with a split personality. Normally, it forms part of the heart's excitation contraction coupling machinery. But when the heart is stressed, JP2 literally splits in two, and sends its N-terminal domain, JP2NT, to the nucleus, where it suppresses transcription of genes involved in fibrosis, hypertrophy, inflammation and other heart failure related processes. However, if this stress is severe or sustained, the protective action of JP2NT is insufficient to halt the progressive failure. This group asked. "What if this N-terminal domain could be ramped up using gene therapy to aid a failing mouse heart?"   Cindy St. Hilaire:        To answer this question, they injected adenoviral vectors encoding JP2NT into mice either before or soon after transaortic constriction, or TAC, tack, which is a method of experimentally inducing heart failure. They found, in both cases, that the injected animals fared better than the controls. Animals injected before TAC showed less severe cardiac remodeling than control mice, while those treated soon after TAC exhibited slower loss of heart function with reduced ventricle dilation and fibrosis. These data suggest that supplementing JP2NT, via gene therapy or other means, could be a promising strategy for treating heart failure. And this data provides a basis for future translational studies.   Cindy St. Hilaire:        The third article I want to share is titled Piezo1 Is a Mechanosensor Channel in Central Nervous System Capillaries. The first and corresponding author is Osama Harraz from the University of Vermont. Neurovascular coupling is the process whereby transient activation of neurons leads to an upsurge in local blood flow to accommodate the increased metabolic needs of the cell. It's known that agents released from active neurons trigger changes in local capillaries that prompt vasodilation, but how these hemodynamic changes are sensed and controlled is not entirely clear. This group suspected that the mechanosensory protein Piezo1, a calcium channel that regulates dilation and constriction of other blood vessels, may be involved. But whether Piezo1 is even found in the microcirculation of the CNS was unknown. This group shows that Piezo1 is present in cortical capillaries of the brain and the retina of the mouse, and that it responds to changes in blood pressure and flow.   Cindy St. Hilaire:        Ex vivo preparations of mouse retina showed that experimentally induced changes in hemodynamics caused calcium transients and related currents within capillary endothelial cells, and that these were dependent on the presence of Piezo1. While it is not entirely clear how Piezo1 influences cerebral blood flow, its pressure induced activation of CNS capillary endothelial cells suggest a critical role in neurovascular coupling.   Cindy St. Hilaire:        The last article I want to share is titled Small Extracellular Vesicles from Brown Adipose Tissue Mediate Exercise Cardioprotection. The first authors are Hang Zhao and Xiyao Chen. And the corresponding authors are Fuyang Zhang and Ling Tao from the Fourth Military Medical University. Regular aerobic exercise is good for the heart and it increases the body's proportion of brown adipose tissue relative to white adipose tissue. This link has led to the idea that brown fat, possibly via its endocrinal activity, might somehow contribute to exercise related cardioprotection. Zhao and colleagues now show that, indeed, brown fat produces extracellular vesicles that are key to preserving heart health. While mice subjected to four weeks of aerobic exercise were better protected against subsequent heart injury than their sedentary counterparts, blocking the production of EVs prior to exercise significantly impaired this protection. Furthermore, injection of brown fat derived EVs into the hearts of mice lessened the impact of subsequent cardiac injury.   Cindy St. Hilaire:        The team went on to identify micro RNAs within the vesicles responsible for this protection, showing that the micro RNAs suppressed an apoptosis pathway in cardiomyocytes. In identifying mechanisms and molecules involved in exercise related cardio protection, the work will inform the development of exercise mimicking treatments for people at risk of heart disease or who are intolerant to exercise.   Cindy St. Hilaire:        Lastly, I want to bring up that the April 29th issue of Circulation Research also contains a short Review Series on pulmonary hypertension, with articles on: The Latest in Animal Models of Pulmonary Hypertension and Right Ventricular Failure, by Olivier Boucherat; Harnessing Big Data to Advance Treatment and Understanding of Pulmonary Hypertension, by Christopher Rhodes and colleagues; New Mutations and Pathogenesis of Pulmonary Hypertension: Progress and Puzzles in Disease Pathogenesis, by Christophe Guignabert and colleagues; Group 3 Pulmonary Hypertension From Bench to Bedside, by Corey Ventetuolo and colleagues; and Novel Approaches to Imaging the Pulmonary Vasculature and Right Heart, by Sudarshan Rajagopal and colleagues; and Understanding the Pathobiology of Pulmonary Hypertension Due to Left Heart Disease, by Jessica Huston and colleagues.   Cindy St. Hilaire:        Today, Dr Patricia Nguyen and Jessica D'Addabbo, from Sanford University, are with me to discuss their study, Human Coronary Plaque T-cells are Clonal and Cross-React to Virus and Self. And this article is in our May 13th issue of Circulation Research. So, Trisha and Jessica, thank you so much for joining me today.   Jessica D'Addabbo:    Thank you for having us.   Patricia Nguyen:         Yes. Thank you for inviting us to your podcast. We're very excited to be here.   Cindy St. Hilaire:        Yeah. And I know there's lots of authors involved in this study, so unfortunately we can't have everyone join us, but I appreciate you all taking the time.   Patricia Nguyen:         This is like a humongous effort by many people in the group, including Roshni Roy Chowdhury, and Xianxi Huang, as well as Charles Chan and Mark Davis. So, we thank you.   Cindy St. Hilaire:        So atherosclerosis, it stems from lipid deposition in the vascular wall. And that lipid deposition causes a whole bunch of things to happen that lead to a chronic inflammatory state. And there's many cells that can be inflammatory. And this study, your study, is really focusing on the role of T-cells in the atherosclerotic plaque. So, before we get into the nitty gritty details of your study, can you share with us, what is it that a T-cell does normally and what is it doing in a plaque? Or rather, let me rephrase that as, what did we know a T-cell was doing in a plaque before your study?   Patricia Nguyen:         So, T-cells, as you know, are members of the adaptive immune system. They are the master regulators of the entire immune system, secreting cytokines and other proteins to attract immune cells to a diseased portion of the body, for example. T-cells have been characterized in plaque previously, mainly with immunohisto chemistry. And their characterization has also been recently performed using single cell technologies. Those studies have been restricted to mainly mirroring studies, studies in mice in their aortic walls, in addition to human carotid arteries. So, it is well known that T cells are found in plaque and a lot of attention has been given to the macrophage subset as the innate immune D. But let's not forget the T-cell because they're actually composed about... 50% in the plaque are T-cells.   Patricia Nguyen:         And we were particularly interested in the T-cell population because we have a strong collaboration with Dr Mark Davis, who's actually the pioneer of T-cell biology and was the first to describe the T-cell receptor alpha beta receptor in his lab in the 1970s. So, he has developed many techniques to interrogate T-cell biology. And our collaboration with him has allowed us and enabled us to perform many of these single cell technologies. In addition, his colleague, Dr Chen, also was pivotal in helping us with the interrogation and understanding of the T-cells in plaque.   Cindy St. Hilaire:        And I think one of the really neat strengths of your study is that you used human coronary artery plaques. So, could you walk us through? What was that like? I collect a lot of human tissue in my lab. I get a lot of aortic valves from the clinic. And it's a lot of logistics. And a lot of times, we're just fixing them, but you are not just fixing them. So, can you walk us through? What was that experimental process from the patient to the Petri dish? And also, could you tell us a little bit about your patient population that you sampled from?   Jessica D'Addabbo:    So, these were coronary arteries that we got from patients receiving a heart transplant. So, they were getting a heart transplant for various reasons, and we would receive their old heart, and someone would help us dissect out the coronary arteries from these. And then, we would process each of these coronary arteries separately. And this happened at whatever hour the hearts came out of the patient.   Jessica D'Addabbo:    So sometime, I was coming in at 3:00 AM with Dr Nguyen and we would be working on these hearts then, because we wanted the samples to be as fresh as possible. So, we would get the arteries. We would digest out the tissue. And then, we would have certain staining profiles that we wanted to look at so that we could put the cells on fax to be able to sort the cells, and then do all the downstream sequencing from there.   Cindy St. Hilaire:        So, in terms of, I don't know, the time when you get that phone call that a heart's coming in to actually getting those single cells that you can either send a fax or send a sequencing, how long did that take, on a good day? Let's talk only about good days.   Jessica D'Addabbo:    Yeah. A lot of factors went into that, sometimes depending on availability of things. But usually, we were ready with all of the materials in advance. So, I'd say it could be anywhere from six to 12 hours, it would take, to get everything sorted. Then, everything after that would happen. But that was just that critical period of making sure we got the cells fresh.   Patricia Nguyen:         So we have to credit the CT surgeons at Stanford for setting up the program or the structure, infrastructure, that enables us to obtain this precious tissue. That is Jack Boyd and Joseph Woo of CT surgery. So, they have enabled human research on hearts by making these tissues available. Because as you know, a transplant... They can say the transplant's happening at 12:00 AM, but it actually doesn't happen until 4:00 AM. And I think it's very difficult for a lab to make that happen all the time. And I think having their support in this paper was critical. And this has allowed us, enabled us, to interrogate kind of the spectrum of disease, especially focusing on T-cells, which are... They make a portion of the plaque, but the plaque itself has not like a million cells that are immune. A lot of them are not immune. So, enabling us to get the tissue in a timely fashion where they're not out of the body for more than 30 minutes enables us to interrogate these small populations of cells.   Cindy St. Hilaire:        That's actually the perfect segue to my next question, which is, how many cells in a plaque were you able to investigate with the single cell analysis? And what was the percentage again of the T-cells in those plaques or in... I guess you looked at different phases of plaque. So, what was that spectrum for the percentage of T-cells?   Patricia Nguyen:         So, for 10X, for example, you need a minimum of 10,000 captured cells. You could do less, but the utility of the 10X is maximized with 10,000. So, many times before the ability to multiplex these tissues, we were doing like capturing 5,000 for example. And the number of cells follows kind of the disease progression, in the sense that as a disease is more severe, you have more immune cells, in general. And it kind of decreases as it becomes more fibrotic and scarred, like calcified. So, it was a bit challenging to get very early just lipid-only cells. And a lot of those, we captured like 3000 or something like that. And efficiency is like 80% perhaps. So, you kind of capture…   Cindy St. Hilaire:        And also, how many excised hearts are going to have early athero? So, it's...   Patricia Nguyen:         Well, there are... nonischemics will have...   Cindy St. Hilaire:        Oh, okay. Okay.   Patricia Nguyen:         So, the range was nonischemic to ischemic.   Cindy St. Hilaire:        Oh great.   Patricia Nguyen:         So, about a portion... I would say one third of the total heart transplants were ischemic. And a lot of them were non ischemic. But as you know, the nonischemic can mix with ischemia. And so, they could have mild to moderate disease in the other arteries, for example, but not severe like 70%/90% obstruction.   Cindy St. Hilaire:        Wow. That's so great. That's amazing. Amazing sample size you have. So T-cell, it's kind of an umbrella term, right? There's many different types of T-cells. And when you start to get in the nitty gritty, they really do have distinct functions. So, what types of T-cells did you see and did you focus on in this study?   Jessica D'Addabbo:    So, the two main types of T-cells are CD4 positive T-cells and CD8 positive T-cells. And we looked at both of these T-cells from patients. We usually sorted multiple plates from each. And then, with 10X, we captured both. But our major finding was actually that the CD8 positive t-cell population was more clonally expanded than the CD4 population, which led us to believe that these cells were more important in the coronary artery disease progression and in the study that we were doing because for a cell to be clonally expanded, it means it was previously exposed to an antigen. And so, if we're finding these T-cells that are clonally expanded in our plaques, then we're hypothesizing that they were likely exposed to some sort of antigen, and then expanded, and then settled into the plaque.   Cindy St. Hilaire:        And when you're saying expansion, are you talking about them being exposed to the antigen in the plaque and expanding there? Or do you think they're being triggered in the periphery and then honing in as a more clonal population?   Patricia Nguyen:         So, that's a great question. And unfortunately, I don't have the answer to that. So basically-   Jessica D'Addabbo:    Next paper, next paper.   Patricia Nguyen:         Exactly. So, we... Interesting to expand on Jessica's answer. Predominantly what was found, as you said, was memory T-cells, so memory T-cells expressing specific markers, so memory versus naive. And these were effector T-cells. And memory meaning they were previously expanded by antigen engagement, and just happened to be in the plaque for whatever reason. We do not know why T-cells specifically are attracted to the plaque, but they are obviously there. And they're in a memory state, if you will. And some of them did display activation markers, which suggested that they clonally expanded to an antigen. What that antigen is, is the topic of another paper. But certainly, it is important to understand that these patients that we recruit, because they were transplant patients, they're not actively infected, right? That is a exclusionary criteria for transplants, right?   Patricia Nguyen:         So, that means these T-cells were there for unclear reasons. Why they're there is unclear. Whether they are your resident T-cells also is unclear, because the definition of resident T-cell still remains controversial. And you actually have to do lineage tracking studies to find out, "Okay, where... Did they come from the bone marrow? Did they come from the periphery? How did they get there?" Versus, "Okay. They were already there and they just expanded, for whatever reason, inside the plaque."   Cindy St. Hilaire:        So, your title... It was a great title, with this provocative statement, "T-cells are clonal and cross react to virus and self." So, tell us a little bit more about this react to virus and self bit. What did your data show?   Jessica D'Addabbo:    So, because of the way we sequenced the T-cell receptor, we were able to have paired alpha and beta chains. And because we knew the HLA type of the patients, we were able to put the sequences that we got out after we sequenced these through an algorithm called GLIPH, which allows us to look at the CDR3 region of the T cell receptor, which is the epitope binding region. And there are certain peptide. They're about anywhere from three to four amino acids long. These are mapped to certain binding specificities to known peptides. And so, basically, we were able to look at which epitopes were most common in our plaques. And we found that after comparing these to other epitopes, that these were actually more binding to virus. Patricia Nguyen:         So let me add to what Jessica stated, and kind of emphasize the value of the data set, if you will. So, this is, I believe, the first study that provides the complete TCR repertoire of coronary plaque, and actually any plaque that I know of, which is special because we know that there is specificity of TCR binding. It's more complicated than the antibody that binds directly from B cells to the antigen, because the T-cells bind processed antigen. So, the antigens are processed by antigen presenting cells like Dendritic cells and macrophages. And they have a specific HLA MHC class that they need to present to. And they need both arms, the antigen epitope and the MHC, to activate the T-cell. So unfortunately, it's not very direct to find the antigen that is actually activating the T-cell because we're only given a piece of it. Right?            Patricia Nguyen:         But we have provided a comprehensive map of all the TCRs that we find in the plaque. And these TCRs have a sequence, an immuno acid sequence. And luckily, in the literature, there is a database of all TCR specificities. Okay. So, armed with our TCR repertoire, we can then match our TCR repertoire with an existing database of known TCR specificities. Surprisingly, the matching TCRs are specific to virus, like flu, EBV and CMB. And also, because this was done in the era of COVID, we thought it would be important to look at the coronavirus database. We did find that there were matches to the coronavirus database. Even though our finding is not specific to SARS, it does lend to some potential mechanistic link there as well.   So, because this is all computational, it is important to validate. So, the importance of validation requires us to put the TCR alpha beta chain into a Jurkat cell, which is a T-cell line that does not have alpha beta chains on it, and then expose it to what we think is the cognate antigen epitote, with the corresponding HLA MHC APC. Because you don't have all those pieces, it will not work. Yes. So importantly, we did find that what we predicted to have the specificity of a flu peptide had specificity to a flu peptide.   Patricia Nguyen:         So then, the important question was, "Okay, these patients aren't infected, right? Why are these things here? Is there a potential cross reactivity with self peptides?"   Patricia Nguyen:         So luckily, our collaborator, Dr Charles Chan, was able to connect us with another computational algorithm that he was familiar with, whereby we were able to take the peptide sequences from the flu and match them with peptide sequencing from proteins that are self and ubiquitous. And we demonstrated, again, these T-cells were activated in vitro. That is why we concluded that there's a potential cross reactivity between self and virus that can potentially lead to thrombosis associated with viral infections. Of course, this all needs to be proved in vivo.   Cindy St. Hilaire:        Sure, sure.   Patricia Nguyen:         It's that first step for other things.   Cindy St. Hilaire:        The other big immune cell that we know is in atherosclerotic plaques and that's macrophages. And they can help to present antigens and things like that. And they also help to chew up the necrotic bits. And so, do you think that this T-cell component is an earlier, maybe disease driving, process or an adaptive process that goes awry as a secondary event? Patricia Nguyen:         So, I'm a fan of the T-cell. So... I'm with team T cell. I would like to think that it is playing an active role in pathology in this case and not a reactive role, in the sense of just being there. I think that the T-cell is actively communicating with other cells within the plaque, and promoting pro fibrotic and pro inflammatory reactions, depending on the T-cell. So, a subset of this paper was looking at kind of the interactions between the T-cell and other cells within the plaque, like macrophages and smooth muscle cells. And as we know, T-cells are activated and they produce cytokines. Those cytokines then communicate to other cells. And we found that, computationally, when you look at the transcriptome, there is a pro-inflammatory signature of the T-cell that resides in the more complex stage. And then, there's an anti-inflammatory signature that kind of resides in the transition between lipid and fibro atheroma, if you will.   Cindy St. Hilaire:        So, do you know, or is it known, how dynamic these populations are? Obviously, the hearts that you got, the samples you got, didn't have active infections. But do you know perhaps even how long ago they happened, or even how soon after there might be an infection or an antigen presented that you could get this expansion? And could that be a real driver of rupture or thrombosis?   Patricia Nguyen:         So, in theory, you would suppose that T-cells expanding and dividing and producing more and more cytokines would then lead to more macrophages coming, more of their production of proteinases that destroy the plaque. Right? So yes, in theory, yes. I think it's very difficult to kind of map the progression of T cell clonality in the current model that we have, because we're just collecting tissues. However, in the future, as organoids become more in science and kind of a primary tissue, where we can... For example, Mark Davis is making organoids with spleen, and also introducing skin to that.   Patricia Nguyen:         And certainly, we could think of an organoid involving the vasculature with immune cells introduced. And so, I think, in the next phase, project 2.0, we can investigate what... like over time, if you could model atherosclerosis and the immune system contribution, T-cells as well as macrophages and other immune cells, you can then kind of map how it happens in humans. Because obviously, mice are different. We know that mice... Actually, the models of transgenic mice do not rupture. It's very hard to make them rupture. Right?   Cindy St. Hilaire:        Well, if you stop feeding them high fat diet, the plaque goes away.   Patricia Nguyen:         For sure, for sure. So I think.. I mean, Mark Davis is a huge proponent of human based research, like research on human tissue. And as a physician scientist, obviously I'm more inclined to do human based research. And Jessica's going to be a physician someday soon. And I'm sure she's more inclined to do human based research. And certainly, the mouse model and in vitro models are great because you can manipulate them. But ultimately, we are trying to cure human diseases.   Cindy St. Hilaire:        Mice are not little humans. That's what we say in my lab. I similarly do a lot of human based stuff and it's amazing how great mice are for certain things, but still how much is not there when we need to really fully recapitulate a disease model.   So, my last question is kind of regarding this autoimmune angle of your findings. And that is, women tend to have more autoimmune diseases than men, but due to the fact that you are getting heart transplants, you've got a whole lot more men in your study than women. I think it was like 31 men to four women. But, I mean, what can you do? It's the nature of heart transplants. But I'm wondering, did you happen to notice...Maybe the sample size perhaps is too small, but were there any differences in the populations of these cells between women and men? And do you think there could be any differences regarding this more prevalence of autoimmune like reactions in women?   Patricia Nguyen:         So, that's an interesting question, but you hit it on the nose when you said "Your sample is defined mainly by men." And in addition, the samples that were women tend to have less disease. And they tend to be nonischemic in etiology. So, I think that kind of restricts our analysis. And perhaps, I guess, future studies could model using female tissues, for example, instead of only male. But the limitation of all human studies is sample availability. And perhaps, human organoid research can be less limited by that. And certainly, mouse research has become more evenly distributed of male and female mice.   Cindy St. Hilaire:        Yeah. Suffice it to say, human research is hard, but you managed to do an amazing and really important study. It was really elegant and well done. Congratulations on what is an epic amount of time. 12-hour experiments are no joke, and really beautiful data. So, thank you so much for joining me today, Dr Nguyen and Miss almost Dr D'Addabbo. Congrats and I'm really looking forward to seeing your future work.   Jessica D'Addabbo:    Thank you so much.   Patricia Nguyen:         Thanks so much.   Jessica D'Addabbo:    Thank you for having us. This is wonderful.   Cindy St. Hilaire:        That's it for the highlights from the April 29th and May 13th issues of Circulation Research. Thank you so much for listening. Please check out the Circ Res Facebook page and follow us on Twitter and Instagram with the handle @Circres and #Discover CircRes. Thank you to our guests: Dr Patricia Nguyen, and soon to be Doctor, Jessica D'Addabbo, from Stanford University.   This podcast was produced by Ishara Ratnayaka, edited by Melissa Stoner, and supported by the editorial team of Circulation Research. Copy text for the highlighted articles was provided by Ruth Williams. I'm your host, Dr Cindy St. Haler. And this is Discover CircRes, you're on the go source for the most exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association 2022. The opinions expressed by the speakers of this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more information, visit aha journals.org.  

Dr. Melissa Johnson of the Sarah Cannon Cancer Center in Nashville, TN talks to us about a multi-center clinical trial utilizing engineered t-cell therapy similar to CAR-T but better known as TRuC-T therapy (stands for TCR Fusion Construct T cells). While CAR-T cell therapy engineers the patient's own T-cells with chimeric antigen receptors (CARs), Truc-t therapy engineers T-cell receptors (TCRs). Dr. Johnson is a thoracic medical oncologist and is the program director of Lung Cancer Research at Sarah Cannon Cancer Center. Learn more about MesoTV at www.curemeso.org/mesotv.

Solid tumors make up 90% of the cases in cancer patients worldwide but the standard of care has not changed in decades. Chemotherapies are still widely used and are non-specific, often with a wide range of negative side effects for the patient. To address this, Dr Felix Lorenz and his team started the Captain T-Cell project. Based at the Max Delbrück Center in Berlin and supported by https://www.go-bio.de/en/index.html (GO-Bio) and https://www.spark-bih.de/ (SPARK Berlin), they are developing a T-cell receptor (TCR) therapy for tackling solid tumors in a targeted and safe manner for cancer patients. TCRs have the ability to target a wide range of antigens and can be expressed intracellularly, which is important for recognizing those antigens that are not transported to the cell surface. Their technology relies on engineering a patient's own T-cells to recognize specific antigens for solid tumors and reinfused back to the patient where they can find and kill the tumor with high specificity. Initially, they are targeting Epstein-Barr Virus antigens that are expressed throughout tumors called by this disease. In this episode of the BioInnovation Spotlight podcast, we ask Felix what technology lies behind the Captain T-Cell project, how it can help transform cancer therapy for patients, and why he wanted to start a company.

In this episode of Talent Talks, Matt Levy reveals the key question you should ask your employees in order to keep them happy. Do you agree? Let us know in the comments. About Our Guest: Have you had a life altering experience? I had one in 2014 and was given 90 days to live…and glad to have proved the doctors wrong! Like many people who have a life altering experience, it changed my outlook forever, and that outlook now fuels my focus on strategic talent acquisition for Kite, a Gilead company, a leader in cancer immunotherapy. I'm super passionate about the cell therapy business where we harness the body's immune system using CAR-T, TCRs and NeoAntigens to fight cancer. When life was teetering on the edge, I thought a lot about what I missed out on in life and in my career. I procrastinated too much, I spent too long paralyzed by the fear of failure and I struggled when faced with adversity. When I thought I was coming to the end of the line, I thought to myself, if I make it through this alive, I am going to embrace and push through my fear, deal with adversity head on and pursue my dreams.I decided right then and there to dedicate my work to cancer immunotherapy (cell therapy; immuno-oncology) as well as inspiring, motivating and coaching executives, mid-career professionals and college graduates to achieve big goals in their work and in their lives. Additionally, I have a strong passion for the life sciences industry which I support through being heavily networked and attending events designed to increase connections in the life sciences community. _____________________________________________________________________________________________ Hope you enjoyed this episode of Talent Talks! Tune in biweekly as we sit down with executives to hear how they acquire talent for their companies. Check out the links below to get additional information: Matt's LinkedIn: https://www.linkedin.com/in/matthewle... Kite Pharma Website: https://www.kitepharma.com GTS Scientific Website: https://gtscareers.com/ Connect with Robb: https://www.linkedin.com/in/r-hoylegts/

Oncotarget Volume 11, Issue 27 published "Clonality and antigen-specific responses shape the prognostic effects of tumor-infiltrating T cells in ovarian cancer" by Tsuji et al. which reported that to delineate the complexity of anti-tumor T-cell responses, the author's utilized a computational method for de novo assembly of sequences from CDR3 regions of 369 high-grade serous ovarian cancers from TCGA, and then applied deep TCR-sequencing for analyses of paired tumor and peripheral blood specimens from an independent cohort of 99 ovarian cancer patients. In the validation cohort, the authors' discovered that patients with low T-cell infiltration but low diversity or focused repertoires had clinical outcomes almost indistinguishable from highly-infiltrated tumors. They also found that the degree of divergence of the peripheral repertoire from the TIL repertoire, and the presence of detectable spontaneous anti-tumor immune responses are important determinants of clinical outcome. Also that the prognostic significance of TILs in ovarian cancer is dictated by T-cell clonality, degree of overlap with peripheral repertoire, and the presence of detectable spontaneous anti-tumor immune response in the patients. These immunological phenotypes defined by the TCR repertoire may provide useful insights for identifying “TIL-low” ovarian cancer patients that may respond to immunotherapy. Dr. Kunle Odunsi from The Center for Immunotherapy as well as The Department of Gynecologic Oncology at Roswell Park Comprehensive Cancer Center said, "The presence of tumor-infiltrating lymphocytes (TILs) is a key determinant of clinical outcome in a wide range of solid tumors including ovarian cancer." High-throughput next-generation sequencing has made it possible to read the entire CDR3 to uniquely identify specific T cell clones and to estimate the absolute frequency of T cell clones in tumor tissue from the copy number of TCR sequences. The importance of TCR repertoire in shaping anti-tumor immunity in ovarian cancer was recently demonstrated using unbiased functional analysis of TCR repertoires from TILs derived from two patients. Tumor reactivity was revealed in 0–5% of tested TCRs indicating that the vast majority of T cells infiltrating ovarian tumors were irrelevant for tumor recognition. To determine how the TCR repertoire of TILs shapes the prognosis of ovarian cancer patients, the authors' utilized a new computational method for de novo assembly of sequences from CDR3 regions using paired-end RNA-seq data from the Cancer Genome Atlas study of high-grade serous ovarian cancers. The author's examined TCR repertoire in the context of the degree of tumor infiltration by T cells, spontaneous immune responses against bona fide TAAs, and clinical outcome. The Odunsi Research Team concluded in their Oncotarget Research Paper that despite these limitations, this study highlights the extraordinary diversity of the T-cell repertoire in ovarian cancer patients, and demonstrates that pre-existing immunity against cancer antigen is a critical prerequisite to correctly understand the prognostic significance of the T-cell repertoire in the tumor and peripheral blood of patients with ovarian cancer. They have distilled TCR repertoire information into candidate biomarkers that may critically influence the prognosis of ovarian cancer patients. Conceptually, ovarian cancers may not fit into the classic paradigm of ?cold' and ?hot' based on the number of T cells they contain, but also by the TCR repertoire information, which serves as a surrogate for tumor recognition. The latest technologies put these prognostic features in clinical reach not only for predicting prognosis but potentially for determining the best immunotherapeutic strategy for each patient. Full text - https://www.oncotarget.com/article/27666/text/ Correspondence to - Kunle Odunsi - kunle.odunsi@roswellpark.org. Keywords - T-cell repertoire, ovarian cancer, tumor immunity

In this podcast moderated by Dr Michael Kalos, Janssen Oncology, you will hear a panel discussion from the 2019 IO Combinations 360° conference. Topic points include: What are the new opportunities in cell therapy for combinations?What the challenges are going to be with the microenvironment?What is being done to engineer cell therapy?How do you develop CARs and TCRs that deliver payloads?How do you manufacture all of this beyond mouse models to figure out how to effectively do this in patients?How do you actually go about designing trials and testing hypothesis?How do you create the regulatory framework to do these types of studies?How do you engage with regulatory agencies to get these things moving? Panelists include: Sharon Benzeno, PhD, MBA, Adaptive BiotechnologiesChaohong Fan, MD, PhD, FDABruce Levine, PhD, University of PennsylvaniaMark Stewart, PhD, Friends of Cancer ResearchBahram Valamehr, PhD, Fate Therapeutics To learn more about the upcoming IO Combinations 360° conference please visit, www.iocombinations360.com

On this month's episode, we discuss our recent meeting with DOHR, our TEAM PAC HD77 Endorsement, our Lobby Day save-the-date, the holiday schedule for state employees, and the P4P schedule for 2020. Plus, we answer your questions about retirement (401(k) & TCRS), compensation, and more. NOTE: After the filming of this video, DOHR announced the percentages for the 2020 P4P rewards. That information is available here: https://tseaonline.org/breaking-2020-pay-for-performance-rewards-announced/

#237: Marissa Young, Head Coach Duke Softball, visits The Coach Roges Show to preview the upcoming inaugural season for Duke Softball.  The Blue Devils will open the 2018 season on Feb. 8th in Boca Raton, Florida.  The team will face host Florida Atlantic twice as well as Ohio State, Michigan State and Boston University.  They will then head home to host the Big Ten/ACC Challenge Feb. 16-18 playing both Penn  State and Purdue twice.  ACC play will open for the Blue Devils Mar. 9-11 in Chapel Hill.  During ACC play, Duke will host Boston College, Louisville, Georgia Tech and Virginia and travel to Pitt, Notre Dame, and Virginia Tech.  Prior to coming to Duke, Young spent two years as an assistant coach at the University of North Carolina.  In the spring of 2015, Young helped the Tar Heels to a 37-16 overall record and a berth in the NCAA Tournament after the squad won 24 contests the prior season. Young's pitchers posted a 3.30 earned run average with 234 strikeouts in 335.1 innings pitched.  Blue Devils Facebook, Blue Devils Twitter, Coach Young Twitter, TCRS Twitter, TCRS Facebook

#235: Connie May, General Manager, Scrap Yard Dawgs, visits The Coach Roges Show to talk about the 2017 NPF Season.  The Dawgs left Nashville and the 2017 NPF Draft with five draft picks Ali Aguilar (Washington), Hannah Flippen (Utah), Nikki Udria (Oregon), MJ Knighten (Nebraska) and Morgan Zerkle (Marshall) who was named the #1 Overall SR in the country by TCRS on 1/30/17.  2017 will also see a new coaching staff in Houston with Texas A&M, Associate Head Coach, Gerry Glasco, leading the helm joined by Jimmy Kolaitis (Oregon) and Joe Guthrie (Bucknell.).  Dawgs Facebook, Dawgs Twitter, Dawgs IG, TCRS Twitter, TCRS Facebook

#234:  Kelley Green, Head Coach, Coastal Carolina University, visits The Coach Roges Show to talk about the upcoming season for CCU.  This will be the first season for CCU as a member of the Sun Belt Conference.  Coastal holds a 21-16 overall record versus Sun Belt opponents facing off against four of the nine schools in program history -- Appalachian State, Georgia Southern, Georgia State and South Alabama. Six of those Sun Belt opponents finished the 2016 season among the NCAA Top 100 RPI.  The Chanticleers open the 2017 season at home on February 10th hosting its annual Kickin' Chicken Classic (Feb. 10-12) tournament. The field includes Alabama, Towson and Youngstown State.  The second weekend, Coastal hosts UNC Greensboro, Rider University and UMKC as part of the Battle at the Beach (Feb. 17-19).  The Chanticleers will open Sun Belt Conference play versus Texas State (Mar. 11-12). Coastal will host four other conference series at home -- Troy (Mar. 25-26), UL Monroe (April 1-2), Georgia State (April 14-15) and Appalachian State (May 5-6).  For its first road trip of the season, Coastal will travel to South Alabama (Mar. 18-19). Other conference road series include Georgia Southern (April 8-9), Texas Arlington (April 22-23) and Louisiana Lafayette (April 29-30).  Chanticleers Twitter, Chanticleers Facebook, Coach Green Twitter, TCRS Twitter, TCRS Facebook, 

#233:  Corey Lyon, Head Coach, University Louisiana-Monore, visits The Coach Roges Show to talk about the upcoming season for the Warhawks.  We also release our 2017 Position for Position Top 10 SRs.  ULM will have 56 regular season games, which includes four non-conference tournaments and nine Sun Belt Conference series.  The season will start with three days of games in Monroe February 10-12.  The Warhawks will begin their conference schedule in March with their first Sun Belt Conference series against UT Arlington. The other conference teams that the Warhawks will face are Georgia Southern, Texas State, Coastal Carolina, Appalachian State, Troy, South Alabama, Georgia State and Louisiana-Lafayette for a total of 27 conference games.  The team qualified for the Sun Belt tournament the last two years finishing in the semifinals in 2015 and the quarterfinals in 2016. Both of those years, the teams were awarded the Sun Belt Conference Team GPA Award.  Those two years also produced 17 wins over teams with an RPI in the top 100 as well as one win versus a team with an RPI in the top 25. Warhawks Twitter, Coach Lyon Twitter, TCRS Twitter, TCRS Facebook, 

#230: Michael Lotief, Head Coach, Louisiana Ragin' Cajuns.  For the third consecutive season, and fourth time in the past five seasons, the Louisiana Ragin' Cajuns softball team will host a NCAA Regional at Lamson Park after being awarded the No. 14 seed in the 2016 NCAA Softball Tournament.  The NCAA Lafayette Regional will feature the top-seeded Ragin' Cajuns (43-7), Texas A&M (37-18), Texas (37-14) and Boston University (28-22). The winner of the regional will play the winner of the NCAA Norman (Okla.) Regional which features No. 3 national seed Oklahoma (47-4), Ole Miss (39-20), Tulsa (35-19) and Wichita State (35-19).  Action in the NCAA Lafayette Regional begins Friday with Texas A&M and Texas at 3:30 p.m. on ESPN2 followed by Louisiana and Boston University at 6 p.m. on ESPNU. A complete listing of times for games on Saturday and Sunday are to be determined.  Cajuns Twitter, Cajuns Facebook, Coach Lotief Twitter, TCRS Twitter, TCRS Facebook,

#229: Mickey Dean, Head Coach, James Madison University.  Colonial Athletic Association champion James Madison earned a No. 7 seed.  Princeton, Longwood and North Carolina for the four-team double-elimination regional. The Harrisonburg Regional will take place Friday, May 20-22 at Veterans Memorial Park. Top-seeded JMU will face fourth-seeded Princeton on Friday while third-seeded Longwood will take on second-seeded North Carolina Friday.  Host JMU holds a 46-4 record after winning all three games as the top seed of the CAA Tournament last weekend.  Senior pitcher/utility Jailyn Ford was named the Most Outstanding Player of the tournament while sophomore pitcher/infielder Megan Good, junior outfielder Taylor Newton and senior catcher Erica Field were named to the All-Tournament Team. Dukes Twitter, Dukes Facebook, Coach Dean Twitter, TCRS Twitter, TCRS Facebook, 

#228: Kenny Gajewski, Head Coach, Oklahoma State University. In this episode of Cowgirls Softball, Coach Gajewski and Coach Roges look back at Tulsa and UConn and discuss the Oklahoma Series.  OSU defeated Tulsa (1-0) and UCONN (8-0).  Against Tulsa, Freeze went the distance in the circle, allowing just two hits while striking out five to earn the win.  Needham went the distance in the circle against UCONN, allowing just one hit while striking out three to earn the victory. Montgomery led the way at the plate for the Cowgirls, going 3-for-4 with three RBI.  OU G1: Sooners won (8-0).  OU G2: Sooners took the game (5-2).  Coach Gajewski and Coach Roges also discuss the results of Selection Sunday.  The Cowgirls (29-24 overall, 6-11 Big 12) will travel to Athens, Ga., for the Georgia Regional. Oklahoma State will take on Northwestern Friday, May 20th on ESPN3 in the first round.  Cowgirls Twitter, Cowgirls Facebook, Coach Gajewski Twitter, TCRS Twitter, TCRS Facebook.

#227: Kenny Gajewski, Head Coach, Oklahoma State University. In this episode of Cowgirls Softball, Coach Gajewski and Coach Roges recap the series against the Kansas Jayhawks.  G1 (10-4 Win): Mikkelson went 3-for-4 with a team high four RBIs.  Lynch put the Cowgirls up 6-4 in the 4th with a three-run RBI double.  Lynch finished 2-for-4 with three RBIs while O'Donnell went 2-for-3 with an RBI.  G2 (11-9 Win):  T5 Lynch blasted a three-run shot putting OSU up 10-9.  Coats earned the win for the Cowgirls, going 3.2 innings in relief while allowing just one run and hit.  G3 (Canceled).  Upcoming Games: Tulsa & UConn at home (Tomorrow 1 & 4PM)  and Oklahoma at home (Friday 6PM) and at Oklahoma (Saturday 2PM).  Cowgirls Twitter, Cowgirls Facebook, Coach Gajewski Twitter, TCRS Twitter, TCRS Facebook.

#226: Shonda Stanton, Head Coach, Marshall University, and Amy Tudor, Head Coach, Western Kentucky University.  The two coaches visit the show to discuss the upcoming series which will be in Bowling Green, KY.  Games will be this Saturday at 1 and 3PM CT and Sunday at 11:30AM.  Marshall enters the weekend (27-24) overall and (11-10) in Conference USA, while WKU enters (16-28) and (7-11).  TCRS Twitter, TCRS Facebook. 

#225: Kenny Gajewski, Head Coach, Oklahoma State University. In this episode of Cowgirls Softball, Coach Gajewski and Coach Roges recap games against Arkansas and UNLV.  Arkansas (4-1 W): Freeze pitched a complete game with 3K's.  Lynch went 3-for-4 with an RBI.  Montgomery and Reasnor started the offense in the 6th with back-to-back RBI doubles.  UNLV G1 (4-1 W):  Freeze earned with "W" with a complete game.  Montgomery went 3-for-3 with two runs.  G2 (11-6 W):  McKee led the way for going 2-for-2 with two RBI and a walk.  Up Next: Kansas on the road Friday's game will air on ESPN3 at 5PM.  Cowgirls Twitter, Cowgirls Facebook, Coach Gajewski Twitter, TCRS Twitter, TCRS Facebook.

#223: Kenny Gajewski, Head Coach, Oklahoma State University. In this episode of Cowgirls Softball, Coach Gajewski and Coach Roges recap games against Central Arkansas and Baylor. OSU defeated Central Arkansas (17-0), while the Baylor series saw the Lady Bears taking games two and three of the series. BU G1: Freeze continued being great in the circle allowing 1 run over 7 innings which came in the 5th.  Offense led by Lynch going 2-for-3.  G2:  Taylor blasted a 2-run shot in B4 to put the lead at 3-2 .  G3:  Freeze didn't allow a run until the 4th.  Up Next: Wednesday Tulsa at home at 6:30 airing on Fox Sports Plus then Texas in Austin with games on LHN at 6, 1 and Noon (Fri, Sat. & Sun). Cowgirls Twitter, Cowgirls Facebook, Coach Gajewski Twitter, TCRS Twitter, TCRS Facebook.

#222:  Jacquie Joseph, Head Coach, Michigan State, visits The Coach Roges Show to bring listeners up to speed on season.  The Spartans will host Michigan tomorrow at home starting at 4:30 before hosting Indiana this weekend with games at 4:00, 1:00 and 1:00 on Friday, Saturday and Sunday.  Saturday will also be Shanin Thomas Day.  The Spartans will then face Michigan and Northwestern on the road before facing Eastern Michigan and Rutgers at home and ending the regular season on the road against Ohio State.  Spartans Twitter, Spartans Facebook, Spartans IG, Coach Joseph Twitter, TCRS Twitter, TCRS Facebook, 

#221: Kenny Gajewski, Head Coach, Oklahoma State University. In this episode of Cowgirls Softball, Coach Gajewski and Coach Roges recap games against Tulsa and Iowa State. OSU fell at Tulsa (0-9) while the Iowa State series saw the Cowgirls come away with the sweep (10-2, 12-10 and 10-2). ISU G1: Taylor Lynch broke the consecutive game hit streak. Freeze went six innings with seven hits, two runs and seven strikeouts. Montgomery finished two-for-four with four RBIs to help lead the Cowgirls to victory. First five hitters in the OSU lineup went 10-for-16 in the game with six RBIs and eight runs scored.  G2: Montgomery went 3-for-4 with five RBIs. Coats went two innings allowing zero runs for the "W."  G3: Mikkelson had walk-off walk in B5. Lynch extended her school-record hit streak. Up Next: Wednesday Central Arkansas on the road then Baylor at home. Cowgirls Twitter, Cowgirls Facebook, Coach Gajewski Twitter, TCRS Twitter, TCRS Facebook.

#220:  Lu Harris-Champer, Head Coach, University of Georgia, visits TCRS to preview the upcoming series against the Missouri Tigers.  Georgia will face Mizzou on the road in Columbia tonight at 7:30 ET (SEC Network +), Saturday at 6 ET (ESPN2) and Sunday at 1 ET (SEC Network +).  The Bulldogs enter the series with an overall record of 31-8 and a SEC record of 5-4 after having swept Texas A&M, winning 1 of 3 against South Carolina and taking 1 of 3 from LSU.  The Tigers enter the series 26-7 overall and 5-4 in the SEC after having taken 2 of 3 from Ole Miss and Tennessee and splitting with Alabama.  Coach Champer Twitter, GA Softball Twitter, GA Softball Facebook, TCRS Twitter, TCRS Facebook

#219: Shelly Hoerner, Head Coach, Georgia Tech, visits TCRS to preview the upcoming series against the Kansas Jayhawks and talk some ACC Softball as well.  This Saturday and Sunday, April 9th and 10th, Tech will face North Texas in addition to the Jayhawks in Lawrence, Kansas.  2016 for Tech has seen (FR) Katie Krzus lead the team offensively, while (FR) Jenna Goodrich has been the team's anchor inside the circle.  Tech with a combined 10 (FR & SO) out of a total 16 person roster has a young squad still trying to find its identity.  In 2015, Hoerner coached the Yellow Jackets to upset victories against No. 20 Nebraska and No. 22 Texas A&M. Maddie Lionberger earned her second career All-Conference honor under Hoerner's wing when she was named All-ACC Second Team. Coach Hoerner Twitter, Tech Softball Twitter, Tech Softball Facebook, TCRS Twitter, TCRS Facebook

#218: Megan Smith, Head Coach, University of Kansas, visits TCRS to preview the upcoming series against Georgia Tech and talk some BIG XII Softball.  Before continuing BIG XII play starting April 15th at home against Texas Tech, the Jayhawks will host both North Texas and Georgia Tech this weekend.  North Texas will face KU Friday at 5 and Saturday at 1:30.  The Jayhawks will then face the Yellow Jackets Saturday at 4 and Sunday at 11:30.  Jayhawks Twitter, Jayhawks Facebook. TCRS Twitter, TCRS Facebook 

#217: Kenny Gajewski, Head Coach, Oklahoma State University.  In this episode of Cowgirls Softball, Coach Gajewski and Coach Roges recap games against Oklahoma and Texas Tech.  OSU went 0-4 this past week falling to Oklahoma (2-10) and then getting swept by Texas Tech (7-9, 18-19 and 7-8).Tiffany Mikkelson hit two home runs to break the school's career record in a 19-18 loss to Texas Tech at Rocky Johnson Field on Saturday. Lynch now has the second-longest streak in program history, second only to Shanel Scott. Scott produced a 17-game hit streak in 2005. Up Next: Oklahoma State stays on the road when it travels to Tulsa for a mid-week game. First pitch is set for 5 p.m. on April 6.  OSU will then return home to continue Big XII play against Iowa State Friday-Sunday at 7, 2 and Noon respectively.  Cowgirls Twitter, Cowgirls Facebook, Coach Gajewski Twitter, TCRS Twitter, TCRS Facebook.

#216:  Jen McIntyre, Head Coach, UConn, visits TCRS.  Coach McIntyre will preview the upcoming series against the University of Central Florida.  The 2016 campaign is McIntyre's second with UConn.  After a mostly mild out of conference tournament schedule which slated games against LSU, South Carolina and Michigan State, the Huskies are ready to battle for the American Athletic Conference Regular Season Championship. Last week AAC play opened for UConn going (1-2) against Memphis on the road.  In order for UConn to be competitive in the AAC, Kayla Doty (JR-Pitcher) out of Ghent, N.Y. is going to have to do a majority of the throwing and emerge as the leader of this staff.  Huskies Twitter, Huskies Facebook, Coach McIntyre Twitter, TCRS Twitter, TCRS Facebook

#215: Kenny Gajewski, Head Coach, Oklahoma State University.  In this episode of Cowgirls Softball, Coach Gajewski and Coach Roges recap games against Wichita State University and Ole Miss.  OSU defeated Wichita State (8-2) in wich Kacey Freeze's ability to change speeds shined in her complete game not allowing a Shocker hit in the final three innings. Shippy, Lynch & Mikkelson combined for six RBI going eight-for-11.  OSU handed Ole Miss two losses (9-6) & (8-6).  G1 was a power hitting showcase as Shippy, Mikkelson, Montogmery and Taylor all hit homers.  G2 was more of a technical game with Shippy, Lynch, Mikkelson, Montgomery and Hughes all getting stolen bases.  Streaks:  Lynch 12 game hitting (Lynch is now batting .412 on the season with 15 RBIs.).  Shippy reached base in 25 straight games.  Previews: Oklahoma and Texas Tech.  Cowgirls Twitter, Cowgirls Facebook, Coach Gajewski Twitter, TCRS Twitter, TCRS Facebook.

#214: Kenny Gajewski, Head Coach, Oklahoma State University.  In this episode of Cowgirls Softball, Coach Gajewski and Coach Roges recap Missouri State and a three-game series against Houston.  Kacy Freeze (6-4) pitched a complete game and gave up just two hits in her second shutout of the season against Missouri State leading OSU to a (4-0) win. The performance was her fifth complete game of the year.  OSU was able to win the series against Houston after falling in game1 (9-10) OSU would defeat Houston (12-3) and (7-3).  During the Houston series, Shippy reached base for a team-high 22 consecutive games, Freshman Taylor Lynch continued her hitting streak, which now stands at nine games. She has also reached base 17 consecutive games and Freeze picked up her seventh win.  Previews: Wichita State & a (DH) against Ole Miss.  Cowgirls Twitter, Cowgirls Facebook, Coach Gajewski Twitter, TCRS Twitter, TCRS Facebook.

#213: Kenny Gajewski, Head Coach, Oklahoma State University.  In this episode of Cowgirls Softball, Coach Gajewski and Coach Roges recap Wichita State University during which Randee O'Donnell's second-inning grand slam lifted OSU to a 4-3 victory.  They also recap the Mizuno Classic: G1 vs Miami: Following the first inning, Freeze retired nine of the next 11 batters allowing only one run while posting six K's in 6.2 IP.  Lynch (2-for-3, 2 RBI, HR) led the way with her third multi-hit performance in her last five games, G2 vs Cleveland State: Mikkelson's fifth homer of the season, leaving her only four shy of the all-time home run record in program history, G3 vs Miami: Lynch (3-for-4), & Shippy (2-for-3).  Previews: Missouri State and Houston.  Cowgirls Twitter, Cowgirls Facebook, Coach Gajewski Twitter, TCRS Twitter, TCRS Facebook.