Podcasts about solid tumors

Biochemist Lingyin Li survived breast cancer at just 30 and now works to harness the human immune system to fight cancers that have long evaded treatment. T cells, she says, are powerful cancer killers, but they can be oblivious. She and her lab colleagues have discovered a masking enzyme that squelches the immune system's “danger signals” and are now developing drugs to block that enzyme. She likens her work to an arms race between cancer and immunotherapy. “The cancers are not getting smarter, but we are,” Li tells host Russ Altman on this episode of Stanford Engineering's The Future of Everything podcast.Have a question for Russ? Send it our way in writing or via voice memo, and it might be featured on an upcoming episode. Please introduce yourself, let us know where you're listening from, and share your question. You can send questions to thefutureofeverything@stanford.edu.Episode Reference Links:Stanford Profile: Lingyin LiConnect With Us:Episode Transcripts >>> The Future of Everything WebsiteConnect with Russ >>> Threads / Bluesky / MastodonConnect with School of Engineering >>> Twitter/X / Instagram / LinkedIn / FacebookChapters:(00:00:00) IntroductionRuss Altman introduces guest Lingyin Li, a professor of biochemistry at Stanford University.(00:03:38) Research MotivationLingyin explains how her breast cancer diagnosis inspired her research.(00:04:31) How T-Cells WorkT-cell mechanisms and why they struggle to reach solid tumors.(00:05:38) Immune System OverviewInnate and adaptive immunity and how mutations make cancer recognizable.(00:07:28) Awakening the Immune SystemEfforts to stimulate innate immune cells to detect and expose tumors.(00:10:54) The Cancer SignalDiscovery of cancer-derived DNA signals that alert the immune system.(00:13:01) Cancer's Evasion MechanismHow tumors destroy immune signals to hide from detection.(00:14:26) ENPP1 EnzymeIdentification of ENPP1 as the enzyme enabling immune evasion.(00:15:22) Balancing Immunity and SafetyRole of ENPP1 in autoimmunity and the challenge of targeting it safely.(00:19:30) ENPP1 InhibitorsDevelopment of molecules to block ENPP1 and enhance immune signaling.(00:24:55) Preclinical FindingsThe promising results against aggressive solid tumors in animal studies(00:28:05) From Lab to ClinicThe progress toward FDA approval and preparation for human testing.(00:31:04) Future In a MinuteRapid-fire Q&A: innovation, collaboration, and the outlook for cancer treatment.(00:33:14) Conclusion Connect With Us:Episode Transcripts >>> The Future of Everything WebsiteConnect with Russ >>> Threads / Bluesky / MastodonConnect with School of Engineering >>>Twitter/X / Instagram / LinkedIn / Facebook Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

In today's episode, we had the pleasure of speaking with J. Thaddeus Beck, MD, FACP, about the FDA approval of pembrolizumab and berahyaluronidase alfa-pmph (subcutaneous pembrolizumab; Keytruda Qlex) for subcutaneous injection in adult and pediatric patients at least 12 years of age with solid tumors for which the intravenous formulation of pembrolizumab (Keytruda) is indicated.

Dr. Hope Rugo and Dr. Giuseppe Curigliano discuss recent developments in the field of bispecific antibodies for hematologic and solid tumors, including strategies to optimize the design and delivery of the immunotherapy. TRANSCRIPT Dr. Hope Rugo: Hello and welcome to By the Book, a podcast series from ASCO that features engaging conversations between editors and authors of the ASCO Educational Book. I am your host, Dr. Hope Rugo. I am the director of the Women's Cancers Program and division chief of breast medical oncology at the City of Hope Cancer Center. I am also the editor-in-chief of the Educational Book. Bispecific antibodies represent an innovative and advanced therapeutic platform in hematologic and solid tumors. And today, I am delighted to be joined by Dr. Giuseppe Curigliano to discuss the current landscape of bispecific antibodies and their potential to reshape the future of precision oncology. Dr. Curigliano was the last author of an ASCO Educational Book piece for 2025 titled, "Bispecific Antibodies in Hematologic and Solid Tumors: Current Landscape and Therapeutic Advances." Dr. Curigliano is a breast medical oncologist and the director of the Early Drug Development Division and chair of the Experimental Therapeutics Program at the European Institute of Oncology in Milan. He is also a full professor of medical oncology at the University of Milan. You can find our disclosures in the transcript of this episode. Dr. Curigliano, Giuseppe, welcome and thanks for being here. Dr. Giuseppe Curigliano: Thanks a lot for the invitation. Dr. Hope Rugo: Giuseppe, I would like to first ask you to provide some context for our listeners on how these novel therapeutics work. And then perhaps you could tell us about recent developments in the field of bispecific antibodies for oncology. We are at a time when antibody-drug conjugates (ADCs) are all the rage and, trying to improve on the targeting of specific antigens, proteins, receptors in the field of oncology is certainly a hot and emerging topic. Dr. Giuseppe Curigliano: So, thanks a lot. I believe really it was very challenging to try to summarize all the bispecific antibodies that are under development in multiple solid tumors. So, the first thing that I would like to highlight is the context and the mechanism of action of bispecific antibodies. Bispecific antibodies represent a groundbreaking advancement in cancer immunotherapy, because these engineered molecules have the unique ability to target and simultaneously bind to two distinct antigens. That is why we call them bispecific. So typically, one antigen is expressed on the tumor cell and the other one is expressed on the immune effectors, like T-cell or natural killer cells. So this dual targeting mechanism offers several key advantages over conventional monoclonal antibodies because you can target at the same time the tumor antigen, downregulating the pathway of proliferation, and you can activate the immune system. So the primary mechanism through which bispecific antibodies exert their therapeutic effects are: First, T-cell redirecting. I mean, many bispecific antibodies are designed to engage tumor-associated antigens like epidermal growth factor receptor, HER2, on the cancer cell and a costimulatory molecule on the surface of T-cell. A typical target antigen on T-cell is CD3. So what does it mean? That you activate the immune system, immune cells will reach the tumor bed, and you have a dual effect. One is downregulating cell proliferation, the other one is activation of the immune system. This is really important in hematological malignancies, where we have a lot of bispecifics already approved, like acute lymphoblastic leukemia or non-Hodgkin lymphoma.  The second, in fact, is the engagement of the tumor microenvironment. So, if you engage immune effector cells like NK cells or macrophages, usually the bispecific antibodies can exploit the immune system's ability to recognize and kill the immune cells, even if there is a lack of optimal antigen presentation.  And finally, the last mechanism of action, this may have a role in the future, maybe in the early cancer setting, is overcoming immune evasion. So bispecific antibodies can overcome some of the immune evasion mechanisms that we see in cancer. For example, bispecific antibodies can target immune checkpoint receptors, like PD-L1 and CTLA-4. Actually, there is a bispecific under development in breast cancer that has a dual targeting on vascular endothelial growth factor receptor and on PD-L1. So you have a dual effect at the same time. So, what is really important, as a comment, is we need to focus first on the optimal format of the bispecific, the optimal half-life, the stability, because of course even if they are very efficient in inducing a response, they may give also a lot of toxicities. So in clinical trials already, we have several bispecifics approved. In solid tumors, very few, specifically amivantamab for non-small cell lung cancer, but we have a pipeline of almost 40 to 50 bispecifics under development in multiple solid tumors, and some of them are in the context of prospective randomized trials. Dr. Hope Rugo: So this is really a fascinating area and it's really exciting to see the expansion of the different targets for bispecific antibodies. One area that has intrigued me also is that some of the bispecifics actually will target different parts of the same receptor or the same protein, but presumably those will be used as a different strategy. It's interesting because we have seen that, for example, in targeting HER2. Dr. Giuseppe Curigliano: Oh, yes, of course. You may consider some bispecifics like margetuximab, I suppose, in which you can target specifically two different epitopes of the same antigen. This is really an example of how a bispecific can potentially be more active and downregulating, let us say, a pathway, by targeting two different domains of a specific target antigen. This is an important point.  Of course, not all the bispecifics work this way, because some of the target antigen may dimerize, and so you have a family of target antigen; an example is epidermal growth factor receptor, in which you have HER1, HER2, HER3, and HER4. So some of them can inhibit the dimerization between one target antigen and the other one, in order to exert a more antiproliferative effect. But to be honest, the new generation of them are more targeting two different antigens, one on the tumor and one on the microenvironment, because according to the clinical data, this is a more efficient way to reduce proliferation and to activate the immune system. Dr. Hope Rugo: Really interesting, and I think it brings us to the next topic, which is really where bispecific antibodies have already shown success, and that is in hematologic malignancies where we have seen very interesting efficacy and these are being used in the clinic already. But the expansion of bispecific antibodies into solid tumors faces some key challenges. It's interesting because the challenges come in different shapes and forms. Tell us about some of those challenges and strategies to optimize bispecific antibody design, delivery, patient selection, and how we are going to use these agents in the right kind of clinical trials. Dr. Giuseppe Curigliano: This is really an excellent question because despite bispecific antibodies having shown a remarkable efficacy in hematological malignancies, their application in solid tumors may have some challenges. The first one is tumor heterogeneity. In hematological malignancy, you have a clear oncogene addiction. Let us say that 90% of the cells may express the same antigen. In solid tumors, it is not the same. Tumor heterogeneity is a typical characteristic of solid tumors, and you have high heterogeneity at the genetic, molecular, and phenotypic levels. So tumor cells can differ significantly from one another, even if within the same tumor. And this heterogeneity sometimes makes it difficult to identify a single target antigen that is universally expressed in an hematological malignancy. So furthermore, sometimes the antigen expressed on a tumor cell can be also present on the normal tissue. And so you may have a cross-targeting. So let's say, if you have a bispecific against epidermal growth factor receptor, this will target the tumor but will target also the skin with a lot of toxicity. The second challenge is the tumor microenvironment. The solid tumor microenvironment is really complex and often immunosuppressive. It is characterized by the presence of immunosuppressor cells like the T regulators, myeloid derived suppressor cells, and of course the extracellular matrix. All these factors hinder immune cell infiltration and also may reduce dramatically the effectiveness of bispecific antibodies. And as you know, there is also an hypoxic condition in the tumor. The other challenge is related to the poor tumor penetration. As you know also with antibody-drug conjugate, only 1 to 3% of the drug will arrive in the tumor bed. Unlike hematological malignancies where tumor cells are dispersed in the blood and easily accessible, the solid tumors have a lot of barriers, and so it means that tumor penetration can be very low. Finally, the vascularity also of the tumor can be different across solid tumors. That is why some bispecifics have a vascular endothelial growth factor receptor or vascular endothelial growth factor as a target. Of course, what do we have to do to overcome these challenges? First, we have to select the optimal antigen. So knowing very well the biology of cancer and the tumor-associated antigens can really select a subgroup of epitopes that are specifically overexpressed in cancer cells. And so we need to design bispecifics according to the tumor type. Second, optimize the antibody format. So there are numerous bispecific antibody formats. We can consider the dual variable domain immunoglobulin, we specified this in our paper. The single chain variable fragments, so FC variable fragments, and the diabodies that can enhance both binding affinity and stability. And finally, the last point, combination therapies. Because bispecific antibodies targeting immune checkpoint, we have many targeting PD-1 or PD-L1 or CTLA-4, combined eventually with other immune checkpoint inhibitors. And so you may have more immunostimulating effect. Dr. Hope Rugo: This is a fascinating field and it is certainly going to go far in the treatment of solid tumors. You know, I think there is some competition with what we have now for antibody-drug conjugates. Do you see that bispecifics will eventually become bispecific ADCs? Are we going to combine these bispecific antibodies with ADCs, with chemotherapy? What is the best combination strategy do you think looking forward? Dr. Giuseppe Curigliano: So, yes, we have a bispecific ADC. We have actually some bispecifics that are conjugated with a payload of chemotherapy. Some others are conjugated with immunoactivation agents like IL-2. One of the most effective strategies for enhancing bispecific activity is the combination therapy. So which type of combination can we do? First, bispecific antibodies plus checkpoint inhibitors. If you combine a bispecific with an immune checkpoint, like anti-PD-1, anti-PD-L1, or anti-CTLA-4, you have more activity because you have activation of T-cells, reduction of immunosuppressive effect, and of course, the capability of this bispecific to potentiate the activity of the immune checkpoint inhibitor. So, in my opinion, in a non-small cell lung cancer with an expression of PD-L1 more than 50%, if you give pembrolizumab plus a bispecific targeting PD-L1, you can really improve both response rate and median progression-free survival.  Another combination is chemotherapy plus bispecific antibodies. Combining chemotherapy with bispecific can enhance the cytotoxic effect because chemotherapy induces immunogenic cell death, and then you boost with a bispecific in order to activate the immune system. Bispecific and CAR T-cells, until now, we believe that these are in competition, but this is not correct. Because CAR T-cells are designed to deliver an activation of the immune system with the same lymphocytes engineered of the patients, with a long-term effect. So I really do not believe that bispecifics are in competition with CAR T-cells because when you have a complete remission induced by CAR T-cell, the effect of this complete remission can last for years. The activity of a bispecific is a little bit different. So there are some studies actually combining CAR T-cells with bispecifics. For example, bispecific antibodies can direct CAR T-cells in the tumor microenvironment, improving their specificity and enhancing their therapeutic effect.  And finally, monoclonal antibody plus bispecific is another next generation activity. Because if you use bispecific antibodies in combination with existing monoclonal antibodies like anti-HER2, you can potentially increase the immune response and enhance tumor cell targeting. In hematological malignancies, this has been already demonstrated and this approach has been particularly effective. Dr. Hope Rugo: That's just so fascinating, the whole idea that we have these monoclonal antibodies and now we are going to add them to bispecifics that we could maybe attach on different toxins to try and improve this, or even give them with different approaches. I suppose giving an ADC with a bispecific would sort of be similar to that idea of giving a monoclonal antibody with the bispecific. So it is certainly intriguing. We also will need to understand the toxicity and cost overall and how we are going to use these, the duration of treatment, the assessment of biomarkers. There are just so many different aspects that still need to be explored.  And then with that idea, can you look ahead five or ten years from now, and tell us how you think bispecific antibodies will shape our next generation cancer therapies, how they will be incorporated into precision oncology, and the new combinations and approaches as we move forward that will help us tailor treatment for patients both with solid tumors and hematologic malignancies? Are we going to be giving these in early-stage disease in solid tumors? So far, the studies are primarily focusing on the metastatic setting, but obviously one of the goals when we have successful treatments is to move them into the early stage setting as quickly as possible. Dr. Giuseppe Curigliano: Let us try to look ahead five years rather than ten years, to be more realistic. So, personally I believe some bispecifics can potentially replace current approaches in specifically T-cell selected population. As we gather more data from ongoing clinical trials and we adopt a deeper understanding of the tumor immuno microenvironment, of course we may have potentially new achievement. A few days ago, we heard that bispecifics in triple negative breast cancer targeting VEGF and PD-L1 demonstrated an improvement in median progression-free survival.  So, how to improve and to impact on clinical practice both in the metastatic and in the early breast cancer setting or solid tumor setting? First, personalized antigen selection. So we need to have the ability to tailor bispecific antibody therapy to the unique tumor profile of individual patients. So the more we understand the biology of cancers, the more we will be able to better target. Second, bispecific antibodies should be combined. I can see in the future a potential trial in which you combine a bispecific anti-PD-L1 and VEGF with immune checkpoint inhibitor selected also to the level of expression of PD-L1, because integration of antibody bispecific with a range of immunotherapies, and this cannot be only immune checkpoint inhibitors, but can be CAR T-cells, oncolytic viruses, also targeted therapy, will likely be a dominant theme in the coming years. This combination will be based on the specific molecular and immuno feature of the cancer of the patient.  Then we need an enhanced delivery system. This is really important because you know now we have a next generation antibody. An example are the bicyclic. So you use FC fragment that are very short, with a low molecular weight, and this short fragment can be bispecific, so can target at the same time a target antigen and improving the immune system. And so the development of this novel delivery system, including also nanoparticles or engineered viral vectors, can enhance the penetration in the tumor bed and the bioavailability of bispecific antibodies. Importantly, we need to reduce toxicity. Until now, bispecifics are very toxic. So the more we are efficient in delivering in the tumor bed, the more we will reduce the risk of toxicity. So it will be mandatory to reduce off-target effects and to minimize toxicity.  And finally, the expansion in new indication. So I really believe you raised an excellent point. We need to design studies in the neoadjuvant setting in order to better understand with multiple biopsies which is the effect on the tumor microenvironment and the tumor itself, and to generate hypotheses for potential trials or in the neoadjuvant setting or in those patients with residual disease.  So, in my opinion, as we refine design, optimize patient selection, and explore new combination, in the future we will have more opportunity to integrate bispecifics in the standard of care. Dr. Hope Rugo: I think it is particularly helpful to hear what we are going to be looking for as we move forward to try and improve efficacy and reduce toxicity. And the ability to engineer these new antibodies and to more specifically target the right proteins and immune effectors is going to be critical, of course, moving forward, as well as individualizing therapy based on a specific tumor biology.  Hearing your insights has been great, and it really has opened up a whole area of insight into the field of bispecifics, together with your excellent contribution to the ASCO Educational Book. Thank you so much for sharing your thoughts and background, as well as what we might see in the future on this podcast today. Dr. Giuseppe Curigliano: Thank you very much for the invitation and for this excellent interview. Dr. Hope Rugo: And thanks to our listeners for joining us today. You will find a link to the Ed Book article we discussed today in the transcript of this episode. It is also, of course, on the ASCO website, as well as on PubMed. Please join us again next month on By the Book for more insightful views on the key issues and innovations that are shaping modern oncology. 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. Hope Rugo  @hope.rugo  Dr. Giuseppe Curigliano @curijoey Follow ASCO on social media:       @ASCO on X (formerly Twitter)       ASCO on Bluesky      ASCO on Facebook       ASCO on LinkedIn       Disclosures:      Dr. Hope Rugo:   Honoraria: Mylan/Viatris, Chugai Pharma  Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer  Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx  Dr. Giuseppe Curigliano: Leadership: European Society for Medical Oncology, European Society of Breast Cancer Specialists, ESMO Open, European Society for Medical Oncology Honoraria: Ellipses Pharma Consulting or Advisory Role: Roche/Genentech, Pfizer, Novartis, Lilly, Foundation Medicine, Bristol-Myers Squibb, Samsung, AstraZeneca, Daiichi-Sankyo, Boerigher, GSK, Seattle Genetics, Guardant Health, Veracyte, Celcuity, Hengrui Therapeutics, Menarini, Merck, Exact Sciences, Blueprint Medicines, Gilead Sciences Speakers' Bureau: Roche/Genentech, Novartis, Pfizer, Lilly, Foundation Medicine, Samsung, Daiichi Sankyo, Seagen, Menarini, Gilead Sciences, Exact Sciences Research Funding: Merck Travel, Accommodations, Expenses: Roche/Genentech, Pfizer, Daiichi Sankyo, AstraZeneca      

A panel of oncology pharmacists discusses the role oflifileucel in metastatic melanoma and other considerations for using cellular therapy in solid tumors. Featuring Brooke Adams, PharmD, BCOP Natalie Brumwell, PharmD, BCOP Bryant A. Clemons, PharmD, BCOP In a special co-branded episode between Oncology On theGo, hosted by CancerNetwork®, and the American Society for Transplantation and Cellular Therapy (ASTCT)'s program, ASTCT Talks, for American Pharmacists Month, a panel of oncology pharmacists discussed optimal strategies for using cellular therapies as treatment for patients with solid tumors. The panel included Brooke Adams, PharmD, BCOP, a board-certified oncology pharmacist specializing in stem cell transplantation and cellular therapy at the Orlando Health Cancer Institute in Orlando, Florida; Natalie Brumwell, PharmD, BCOP, a board-certified oncology pharmacist specializing in cellular therapy at Memorial Sloan Kettering Cancer Center in New York, New York; and Bryant A. Clemons, PharmD, a board-certified oncology pharmacist specializing in hematology, blood and marrow transplantation, and cellular therapy at the University of Kentucky's Markey Cancer Center in Lexington, Kentucky. The discussion focused on the use of the first commercially available tumor-infiltrating lymphocytes (TILs) for patients with unresectable or metastatic melanoma, lifileucel (Amtagvi), which the FDA granted accelerated approval status to in February 2024.1 The panelists first reviewed supporting data from the phase 2 C-144-01 trial (NCT02360579), in which lifileucel demonstrated an objective response rate of 31.5% (95% CI, 21.1%-43.4%), and a median duration of response that was not reached (NR; 95% CI, 4.1 months-NR) at the time of the approval. Additionally, the group highlighted considerations for dosinginterleukin-2 (IL-2), including management of toxicities and when to hold or discontinue further doses. Following a thorough breakdown of the proper conditions for using lifileucel in melanoma, the panelists concluded by discussing how to build upon an “exciting time for cellular therapy in solid tumors.” As part of optimizing the dosing of lifileucel and other cellular therapies in these patient populations, the experts exchanged ideas on how practices can collaborate across institutions and departments to expand access to novel treatments while helping providers develop comfort in administering these agents. Reference FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma. News release. FDA. February 16, 2024. Accessed September 30, 2025. https://tinyurl.com/2kweca6x 

In this inspiring episode, Dr. Felipe Gálvez-Cancino, group leader at Oxford's Center for Immuno-Oncology, walks us through his team's groundbreaking research on macrophages, T cells, and immune regulation in solid tumors. Tracing his path from early cancer vaccine work to advanced antibody-dependent cellular phagocytosis (ADCP), Felipe shares how his team is working to reprogram tumor-associated macrophages to more efficiently eliminate cancer cells.He explains how regulatory CD4+ T cells suppress both T cell and macrophage responses within tumors and how removing that suppression can supercharge phagocytic function. We also hear how his lab is leveraging mouse models of hepatocellular carcinoma, clinical samples, and modern molecular biology techniques (like in vivo liver transfection and CRISPR-ready plasmid engineering) to study intratumor heterogeneity and antigen spreading.Felipe also reflects on the value of early molecular biology training—like mastering gigapreps—and emphasizes the importance of curiosity, persistence, and collaboration in scientific careers. Whether you're interested in cancer biology, immunotherapy, or just passionate about translating discoveries into new therapies, this episode offers both technical depth and motivational insight. Subscribe to get future episodes as they drop and if you like what you're hearing we hope you'll share a review or recommend the series to a colleague.  Visit the Invitrogen School of Molecular Biology to access helpful molecular biology resources and educational content, and please share this resource with anyone you know working in molecular biology. For Research Use Only. Not for use in diagnostic procedures.

In a special co-branded episode between Oncology On the Go, hosted by CancerNetwork®, and the American Society for Transplantation and Cellular Therapy (ASTCT)'s program, ASTCT Talks, for American Pharmacists Month, a panel of oncology pharmacists discussed optimal strategies for using cellular therapies as treatment for patients with solid tumors. The panel included Brooke Adams, PharmD, BCOP, a board-certified oncology pharmacist specializing in stem cell transplantation and cellular therapy at the Orlando Health Cancer Institute in Orlando, Florida; Natalie Brumwell, PharmD, BCOP, a board-certified oncology pharmacist specializing in cellular therapy at Memorial Sloan Kettering Cancer Center in New York, New York; and Bryant A. Clemons, PharmD, a board-certified oncology pharmacist specializing in hematology, blood and marrow transplantation, and cellular therapy at the University of Kentucky's Markey Cancer Center in Lexington, Kentucky. The discussion focused on the use of the first commercially available tumor-infiltrating lymphocytes (TILs) for patients with unresectable or metastatic melanoma, lifileucel (Amtagvi), which the FDA granted accelerated approval status to in February 2024.1 The panelists first reviewed supporting data from the phase 2 C-144-01 trial (NCT02360579), in which lifileucel demonstrated an objective response rate of 31.5% (95% CI, 21.1%-43.4%), and a median duration of response that was not reached (NR; 95% CI, 4.1 months-NR) at the time of the approval. Additionally, the group highlighted considerations for dosing interleukin-2 (IL-2), including management of toxicities and when to hold or discontinue further doses.  Following a thorough breakdown of the proper conditions for using lifileucel in melanoma, the panelists concluded by discussing how to build upon an “exciting time for cellular therapy in solid tumors.” As part of optimizing the dosing of lifileucel and other cellular therapies in these patient populations, the experts exchanged ideas on how practices can collaborate across institutions and departments to expand access to novel treatments while helping providers develop comfort in administering these agents. Reference FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma. News release. FDA. February 16, 2024. Accessed September 30, 2025. https://tinyurl.com/2kweca6x

Ming-Wei Chen and Fangheng Zhou, the scientists behind RephImmune, join hosts Lynnsey and Matthew to discuss how their biotech startup is developing a next-generation cell therapy platform designed to overcome the limitations of CAR-T.  With a focus on ovarian cancer, RephImmune's RACE-T technology targets solid tumors by re-engineering immune cells to better locate, penetrate, and survive in the harsh tumor environment. Ming-Wei and Fangheng share their personal motivations, the science behind their approach, and how programs like SCbio DRIVE are helping them move closer to clinical trials. Tune in now!

Sabah Oney, CEO of Philadelphia and San Francisco-based Dispatch Biotherapeutics, on engineering CAR-T cells that can kill solid tumors.

BUFFALO, NY - July 29, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on July 25, 2025, titled “Comprehensive genomic profiling of over 10,000 advanced solid tumors.” In this study, led by Jean-Paul De La O from Exact Sciences Corporation, researchers analyzed data from over 10,000 solid tumor samples from patients with advanced cancer and found that more than 90 percent contained genetic changes that could guide treatment. This work demonstrates the growing impact of large-scale tumor DNA and RNA testing on patient care. The researchers retrospectively analyzed OncoExTra assay information for 31 types of cancer, including breast, colorectal, prostate, lung, and ovarian cancers. Their analysis revealed that nearly a third of patients had alterations associated with approved drugs for their specific cancer, while another third had changes linked to therapies approved for other cancers. These results show that detailed genetic profiling could expand treatment choices. “Biomarkers associated with on- or off-label FDA-approved therapies were detected in 29.2% and 28.0% of samples, respectively.” Another relevant discovery was that many important mutations occurred at very low levels, which are often missed by simpler tests. By using a broad and highly sensitive approach, the scientists were able to identify these rare mutations. They also reported that 7.5 percent of samples carried gene fusions, unusual genetic events that can drive cancer growth. Such findings can be critical in selecting therapies that specifically target these abnormalities. The study also highlighted the value of RNA sequencing in detecting fusion events that traditional DNA tests might miss. Prostate cancer and certain sarcomas showed particularly high rates of these fusion alterations. This type of information can refine cancer diagnosis and improve therapy planning. In addition, the researchers identified changes in several major cancer-related pathways, including those that control cell growth, DNA repair, and immune system response. Alterations in these pathways can point to newer treatment options, such as immunotherapy or drugs designed to block specific cell signals. Overall, this study shows that comprehensive genomic profiling can guide more personalized cancer care by identifying mutations, gene fusions, and other molecular patterns. Advanced testing methods like the OncoExTra assay reveal treatment opportunities even in advanced cancers, ensuring that subtle but important genetic changes are detected. DOI - https://doi.org/10.18632/oncotarget.28757 Correspondence to - Jean-Paul De La O - jdelao@exactsciences.com Video short - https://www.youtube.com/watch?v=awiRhDfiMTE Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28757 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, solid tumors, comprehensive genomic profiling, matched therapy, gene fusions, limit of detection 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

For the first time CAR-T cells, a highly activated type of immune cell, have been used with some success to treat stomach cancer, a so-called solid tumor. William Nelson, director of the Kimmel Cancer Center at Johns Hopkins, says solid … Why has it been so hard to use CAR-T cells to treat solid tumors? Elizabeth Tracey reports Read More »

You've probably heard of CAR-T cells, a type of immune cells taken from someone's body, grown up in a lab and trained to attack their cancer. CAR-Ts are known to be good for treating blood cancers like leukemia, and for … Will solid tumors now be treated with CAR-T cells? Elizabeth Tracey reports Read More »

Please visit answersincme.com/DDP860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, an expert in oncology discusses human epidermal growth factor receptor 3 (HER3)–directed antibody–drug conjugates (ADCs) for the treatment of patients with advanced solid tumors. Upon completion of this activity, participants should be better able to: Explain the rationale for the pan-tumor use of HER3-directed treatment for patients with locally advanced or metastatic solid tumors; Review clinical trials of investigational HER3-directed ADCs in previously treated patients with advanced solid tumors; and Outline criteria that may guide the selection of HER3-directed ADCs to treat advanced solid tumors, based on available evidence.

BUFFALO, NY – June 20, 2025 – A new #review was #published in Volume 16 of Oncotarget on June 10, 2025, titled “Beyond DNA damage response: Immunomodulatory attributes of CHEK2 in solid tumors.” In this paper, led by first author Helen Qian and corresponding author Crismita Dmello from Northwestern University Feinberg School of Medicine, researchers compiled growing evidence that the CHEK2 gene, long known for its role in repairing DNA damage, may also influence how tumors respond to immunotherapy. Their analysis suggests that problems in CHEK2 function might make cancer cells more vulnerable to immune system attacks, highlighting a new opportunity to improve treatment outcomes in solid tumors. Immune checkpoint inhibitors (ICIs) have transformed cancer treatment; however, they are effective in only a subset of patients. This review suggests that tumors with reduced CHEK2 activity may accumulate more mutations that produce signals the immune system can recognize. These signals, known as neoantigens, help immune cells identify and destroy cancer cells more effectively. The review connects this process not only to CHEK2's established role in the DNA damage response but also to a newly proposed function in shaping the immune environment of tumors. CHEK2 normally helps maintain genomic stability by enabling precise DNA repair. When this function is lost, cells rely on more error-prone repair methods, leading to additional mutations. These mutations can increase tumor mutational burden, which has been linked to better outcomes with immunotherapy. Beyond DNA repair, the review highlights a second mechanism: activation of the cGAS-STING pathway. This pathway detects fragments of damaged DNA and triggers inflammation that attracts immune cells to the tumor. The authors highlight studies where CHEK2-deficient tumors responded better to PD-1 inhibitors, a common type of immune checkpoint inhibitor. In both lab models and early-stage clinical settings, CHEK2 loss was associated with increased infiltration of CD8+ T cells—immune cells essential for attacking cancer cells. In cancers such as glioblastoma and renal cell carcinoma, which are typically resistant to immunotherapy, reduced CHEK2 expression was linked with more favorable immune activity and higher expression of interferon-related genes. The compiled evidence points to CHEK2 as a potential biomarker for identifying patients likely to respond to immunotherapy. In addition, combining CHEK2 inhibitors with existing immunotherapies may enhance anti-tumor effects, particularly in cancers with limited treatment options. The review notes that some clinical trials using the CHEK1/2 inhibitor prexasertib alongside immune checkpoint therapies have already shown promising early results. “The initial results from this Phase I clinical trial support the immunomodulatory role of CHEK2 expression and even suggest CHEK2 potentiates immunosuppression.” Although more research is needed to confirm these mechanisms and improve treatment approaches, this review underscores the expanding role of DNA repair genes like CHEK2—not only in maintaining genome integrity but also in helping the immune system fight cancer. DOI - https://doi.org/10.18632/oncotarget.28740 Correspondence to - Crismita Dmello - stellacpak@outlook.com Video short - https://www.youtube.com/watch?v=C26pEBc0itk Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ 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

This week on The Beat, CTSNet Editor-in-Chief Joel Dunning speaks with Dr. Nina Fuller-Shavel, co-chair of the British Society for Integrative Oncology (BSIO) from 2021 to 2023 and current co-chair of the BSIO Clinical Practice and Education Committee, about integrative oncology. Chapters 00:00 Intro 01:29 Integrative Medicine 09:13 Bar Dislocation, Pectus 10:53 Effective Circulating Volume Fraction 13:14 Repair vs Replacement, Edge-to-Edge 16:14 Relaxed TAVI Age Threshold? 18:14 Supravalvar Aortic Stenosis Transaxillary 20:09 How-To, AAE Tricuspid Repair 21:49 Modified Robotic Tracheobronchoplasty 23:34 Dr. Fuller-Shavel, Integrative Oncology 56:21 Upcoming Events 58:28 Closing They discuss what integrative oncology entails, mistletoe therapy, oncothermia, and the innovative integrative oncology app called Oncio. They also explore guidelines relating to this topic, nutrition, and immune checkpoint inhibitors. Dr. Fuller-Shavel also provides recommendations for supporting patients' mindfulness during cancer treatment.   Joel also highlights recent JANS articles on bar dislocation after pectus excavatum repair, effective circulating volume fraction in Type A aortic dissection, surgical mitral valve repair vs replacement after failed mitral transcatheter edge-to-edge repair, and if the age threshold for TAVI can be relaxed to below 65 years.   In addition, Joel explores minimally invasive transaxillary repair of supravalvar aortic stenosis, how to perform an aortic annulus enlargement with tricuspid repair, and modified robotic-assisted tracheobronchoplasty in a patient with severe calcific mediastinal lymphadenopathy. Before closing, he highlights upcoming events in CT surgery.    JANS Items Mentioned  1.) Bar Dislocation After Pectus Excavatum Repair: A Systematic Review of Risk Factors, Stabilization Techniques, and Management Strategies  2.) The Effective Circulating Volume Fraction in Type A Aortic Dissection: A New Risk Factor?   3.) Surgical Mitral Valve Repair vs Replacement After Failed Mitral Transcatheter Edge-to-Edge Repair: The CUTTING-EDGE Registry  4.) Could the Age Threshold for TAVI be Relaxed to Below 65 Years? Pros and Cons  CTSNet Content Mentioned  1.) Minimally Invasive Transaxillary Repair of Supravalvar Aortic Stenosis  2.) How to Perform an Aortic Annulus Enlargement With Tricuspid Repair  3.) Modified Robotic-Assisted Tracheobronchoplasty in a Patient With Severe Calcific Mediastinal Lymphadenopathy  Other Items Mentioned  1.) British Society for Integrative Oncology   2.) National Center for Integrative Oncology    3.) Integrative Oncology Approaches to Supporting Immune Checkpoint Inhibitor Treatment of Solid Tumors  4.) Aortic Valve Replacement Series   5.) Career Center    6.) CTSNet Events Calendar  Disclaimer The information and views presented on CTSNet.org represent the views of the authors and contributors of the material and not of CTSNet. Please review our full disclaimer page here.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC information, and to apply for credit, please visit us at PeerView.com/KAQ865. CME/MOC credit will be available until May 27, 2026.From Innovation to Implementation: Unlocking the Full Potential of Antibody-Drug Conjugates in Solid Tumors In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC information, and to apply for credit, please visit us at PeerView.com/KAQ865. CME/MOC credit will be available until May 27, 2026.From Innovation to Implementation: Unlocking the Full Potential of Antibody-Drug Conjugates in Solid Tumors In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC information, and to apply for credit, please visit us at PeerView.com/KAQ865. CME/MOC credit will be available until May 27, 2026.From Innovation to Implementation: Unlocking the Full Potential of Antibody-Drug Conjugates in Solid Tumors In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC information, and to apply for credit, please visit us at PeerView.com/KAQ865. CME/MOC credit will be available until May 27, 2026.From Innovation to Implementation: Unlocking the Full Potential of Antibody-Drug Conjugates in Solid Tumors In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC information, and to apply for credit, please visit us at PeerView.com/KAQ865. CME/MOC credit will be available until May 27, 2026.From Innovation to Implementation: Unlocking the Full Potential of Antibody-Drug Conjugates in Solid Tumors In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC information, and to apply for credit, please visit us at PeerView.com/KAQ865. CME/MOC credit will be available until May 27, 2026.From Innovation to Implementation: Unlocking the Full Potential of Antibody-Drug Conjugates in Solid Tumors In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC information, and to apply for credit, please visit us at PeerView.com/KAQ865. CME/MOC credit will be available until May 27, 2026.From Innovation to Implementation: Unlocking the Full Potential of Antibody-Drug Conjugates in Solid Tumors In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC information, and to apply for credit, please visit us at PeerView.com/KAQ865. CME/MOC credit will be available until May 27, 2026.From Innovation to Implementation: Unlocking the Full Potential of Antibody-Drug Conjugates in Solid Tumors In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

In today's episode, supported by Exact Sciences, we had the pleasure of speaking with Eric Christenson, MD, about the Oncodetect test, which is available for use in molecular residual disease detection in patients with solid tumors. Dr Christenson is an assistant professor of oncology at the Johns Hopkins School of Medicine in Baltimore, Maryland. In our exclusive interview, Dr Christenson discussed the capabilities of Oncodetect, its clinical applications, key findings from the Alpha-CORRECT study, and the prognostic value of this test.

Daniel Getts, the CEO and Founder of Myeloid Therapeutics is focused on the role of myeloid cells in the immune response to solid tumors. These cells are the first responders in the immune system and play a crucial role in bridging the innate and adaptive immune response. The Myeloid Therapeutics' mRNA technology activates myeloid cells in tumors, making the tumor microenvironment hot and attracting other immune cells to fight the cancer. Daniel explains, "The ability to harness our immune systems has revolutionized how we treat cancer. Unfortunately, we still have a long way to go, and if you think about some of the worst of the worst cancers, such as pancreatic cancer, liver cancer, and so on, immunotherapy has still not gotten us to a place where we can solve this. It's our mission at Myeloid Therapeutics to overcome these challenges. We've uncovered a lot of really interesting things about these cancers in the last 20 years, and we've been harnessing that knowledge."  "Myeloid cells are at the heart of the immune system. They're the first responders. So, if you have an infection or bump your knee, these cells are immediately called to the site to wall off and prevent any more damage. However, they also serve as the bridge to adaptive immunity, the T cells and the B cells, which are also important for integrating an immune response. In the context of COVID vaccines, we talk about antibodies and T cells, it's the myeloid cells that are essential. In the context of what we've been learning, immunotherapy, up until recently, had been very focused on T cells and how to short-circuit the whole system just by using or activating those cells to kill cancer. And what we're starting to learn is to harness the full capability of our own immune systems, you've got to go back to the start. You've got to harness the myeloid compartment so you can orchestrate all immune elements to kill cancer." #MyeloidTherapeutics #MyeloidCells #ImmuneSystem #SolidTumors #Cancer #ImmuneResponse #Oncology #TumorMicroenvironment myeloidtx.com Download the transcript here

Daniel Getts, the CEO and Founder of Myeloid Therapeutics, is focused on the role of myeloid cells in the immune response to solid tumors. These cells are the first responders in the immune system and play a crucial role in bridging the innate and adaptive immune response. The Myeloid Therapeutics' mRNA technology activates myeloid cells in tumors, making the tumor microenvironment hot and attracting other immune cells to fight the cancer. Daniel explains, "The ability to harness our immune systems has revolutionized how we treat cancer. Unfortunately, we still have a long way to go, and if you think about some of the worst of the worst cancers, such as pancreatic cancer, liver cancer, and so on, immunotherapy has still not gotten us to a place where we can solve this. It's our mission at Myeloid Therapeutics to overcome these challenges. We've uncovered a lot of really interesting things about these cancers in the last 20 years, and we've been harnessing that knowledge."  "Myeloid cells are at the heart of the immune system. They're the first responders. So, if you have an infection or bump your knee, these cells are immediately called to the site to wall off and prevent any more damage. However, they also serve as the bridge to adaptive immunity, the T cells and the B cells, which are also important for integrating an immune response. In the context of COVID vaccines, we talk about antibodies and T cells, it's the myeloid cells that are essential. In the context of what we've been learning, immunotherapy, up until recently, had been very focused on T cells and how to short-circuit the whole system just by using or activating those cells to kill cancer. And what we're starting to learn is to harness the full capability of our own immune systems, you've got to go back to the start. You've got to harness the myeloid compartment so you can orchestrate all immune elements to kill cancer." #MyeloidTherapeutics #MyeloidCells #ImmuneSystem #SolidTumors #Cancer #ImmuneResponse #Oncology #TumorMicroenvironment myeloidtx.com Listen to the podcast here

Will Ho, President, CEO, and Co-Founder of IN8bio, a company developing next-generation cellular therapies using gamma delta T cells, which play a unique role in bridging the innate and adaptive immune systems. GDT cell therapies may have reduced side effects compared to other T cell therapies as they can more selectively target tumor cells while sparing healthy tissue. IN8bio is conducting clinical trials using autologous and allogeneic gamma delta T cells for leukemia and glioblastoma with the goal of eliminating the cancer.   Will explains, "As you probably are aware, our immune system is generally broken down into two halves. One is the innate or the immediate portion of the system, which is why we're called IN8bio, the gamma delta T cells, which are considered innate immune cells. On the other, the adaptive is the memory part of our immune system. The gamma delta T cells bridge between both the innate and the adaptive. They actually have features across both. In particular, one of their natural functions is actually to discriminate and to distinguish between those cells that are healthy and safe versus those that are transformed or should be eliminated. That's the very challenge of cancer cells. At the end of the day, they're our own cells, and the gamma delta T cells have a unique ability to distinguish between what should be safe and left alone versus those cells that they should kill." "With the CAR T therapies, we have genetically engineered specific targets such as CD 19 or DPMA into an alpha-beta T cell - somewhat of a release and let it go. Those cells go and seek out every cell in the body that expresses its specific target and kills it. I kind of half-heartedly joke that it's a little bit like Terminator- once you let it go, it seeks its target to try to kill it, no matter the secondary damage. In many cases, we've had numerous toxicities, some of which have resulted in patient death. The gamma delta T cells are more nuanced in its approach. We have created CAR T, specifically for the biology of gamma delta T cells." "Early preclinical work shows they can discriminate between the leukemic cells that should be eliminated and the healthy tissue. This will become increasingly important as we try to target solid tumors. Solid tumors is a market that's nine times bigger than that of leukemias and lymphomas. It's challenging because the tumors, at the end of the day, are intertwined in an organ. Most likely, we need to keep those organs, whether they're your brain like in glioblastoma that we're targeting, or lung cancer or pancreatic cancer and others, we need to be able to discriminate and pick out the healthy tissue versus the tumor tissue because we can't just completely ablate the organ."  #IN8bio #CancerZero #Immunotherapy #Immunology #CancerResearch #TCellEngagers #GDTCells #CART #CellTherapy #GeneTherapy #Pharmaceuticals #BioTech #ClinicalResearch IN8bio.com Download the transcript here  

Will Ho, President, CEO, and Co-Founder of IN8bio, a company developing next-generation cellular therapies using gamma delta T cells, which play a unique role in bridging the innate and adaptive immune systems. GDT cell therapies may have reduced side effects compared to other T cell therapies as they can more selectively target tumor cells while sparing healthy tissue. IN8bio is conducting clinical trials using autologous and allogeneic gamma delta T cells for leukemia and glioblastoma with the goal of eliminating the cancer.   Will explains, "As you probably are aware, our immune system is generally broken down into two halves. One is the innate or the immediate portion of the system, which is why we're called IN8bio, the gamma delta T cells, which are considered innate immune cells. On the other, the adaptive is the memory part of our immune system. The gamma delta T cells bridge between both the innate and the adaptive. They actually have features across both. In particular, one of their natural functions is actually to discriminate and to distinguish between those cells that are healthy and safe versus those that are transformed or should be eliminated. That's the very challenge of cancer cells. At the end of the day, they're our own cells, and the gamma delta T cells have a unique ability to distinguish between what should be safe and left alone versus those cells that they should kill." "With the CAR T therapies, we have genetically engineered specific targets such as CD 19 or DPMA into an alpha-beta T cell - somewhat of a release and let it go. Those cells go and seek out every cell in the body that expresses its specific target and kills it. I kind of half-heartedly joke that it's a little bit like Terminator- once you let it go, it seeks its target to try to kill it, no matter the secondary damage. In many cases, we've had numerous toxicities, some of which have resulted in patient death. The gamma delta T cells are more nuanced in its approach. We have created CAR T, specifically for the biology of gamma delta T cells." "Early preclinical work shows they can discriminate between the leukemic cells that should be eliminated and the healthy tissue. This will become increasingly important as we try to target solid tumors. Solid tumors is a market that's nine times bigger than that of leukemias and lymphomas. It's challenging because the tumors, at the end of the day, are intertwined in an organ. Most likely, we need to keep those organs, whether they're your brain like in glioblastoma that we're targeting, or lung cancer or pancreatic cancer and others, we need to be able to discriminate and pick out the healthy tissue versus the tumor tissue because we can't just completely ablate the organ."  #IN8bio #CancerZero #Immunotherapy #Immunology #CancerResearch #TCellEngagers #GDTCells #CART #CellTherapy #GeneTherapy #Pharmaceuticals #BioTech #ClinicalResearch IN8bio.com Listen to the podcast here  

“The most effective therapies for solid tumors are also the most toxic — and we need to fix that,” says Dr. John Connolly, chief scientific officer of the Parker Institute for Cancer Immunotherapy. In this episode of the Vanguards of Health Care podcast, Connolly tells Bloomberg Intelligence pharmaceutical analyst Sam Fazeli why managing toxicity is the key to unlocking CAR-T’s potential in solid tumors. They explore the rise of in vivo cell therapies, evolving views on the tumor microenvironment and why foundational cancer vaccines may shape the future of all immunotherapy. Connolly also shares the clinical trials he’s watching closely, the ones that could flip the script on cancer care.See omnystudio.com/listener for privacy information.

Robert Den, Chief Medical Officer at Alpha Tau Medical, is changing cancer treatment using their Alpha DaRT technology to deliver a potent form of alpha radiation directly into solid tumors with minimal side effects. There is potential for the Alpha DaRT to be combined with immunotherapy and chemotherapy to further invoke an immune response. This one-time alpha radiation treatment has shown the ability to treat all solid tumors, only limited by the ability to deliver the Alpha DaRT directly to the tumor. Robert explains, "So alpha radiation is one of the three types of radiation that occur naturally, and it's been known as a very potent form of radiation for several decades now. The challenge with alpha radiation in the treatment of patients with localized disease and with solid tumors, meaning tumors not like leukemias or lymphomas but more like pancreas, lung, and prostate cancer, is that the alpha particles themselves aren't only able to travel a very short distance inside tissue or inside the cancer itself." "Before Alpha Tau and the Alpha DaRT technology, there was no pragmatic way to use this super potent and very safe type of radiation because you could not put enough alpha particles inside a tumor to cover the tumor with the radiation dose. What Alpha DaRT technology does is rely on the movement of what's called alpha-emitting daughter atoms." "So essentially, we take a biocompatible inert metal seed, which means that if you were to put this seed into the body, there would be no immune effect. Patients could have it inside them for the entirety of their life. Essentially, what we do is we cover this seed with a radiopharmaceutical called Radium-224. We just put Radium-224 on the outside of the seed. Then, we insert it either through a minimally invasive approach or using a different endoscopic approach inside the tumor directly. So now we have the seed covered with the radium inside the tumor, and this is basically where the magic happens."   #AlphaTauMedical #Cancer #TargetedRadiation #ClinicalResearch #RadiationOncology #Oncology #CancerTreatment #AlphaRadiation  alphatau.com Download the transcript here

Robert Den, Chief Medical Officer at Alpha Tau Medical, is changing cancer treatment using their Alpha DaRT technology to deliver a potent form of alpha radiation directly into solid tumors with minimal side effects. There is potential for the Alpha DaRT to be combined with immunotherapy and chemotherapy to further invoke an immune response. This one-time alpha radiation treatment has shown the ability to treat all solid tumors, only limited by the ability to deliver the Alpha DaRT directly to the tumor. Robert explains, "So alpha radiation is one of the three types of radiation that occur naturally, and it's been known as a very potent form of radiation for several decades now. The challenge with alpha radiation in the treatment of patients with localized disease and with solid tumors, meaning tumors not like leukemias or lymphomas but more like pancreas, lung, and prostate cancer, is that the alpha particles themselves aren't only able to travel a very short distance inside tissue or inside the cancer itself." "Before Alpha Tau and the Alpha DaRT technology, there was no pragmatic way to use this super potent and very safe type of radiation because you could not put enough alpha particles inside a tumor to cover the tumor with the radiation dose. What Alpha DaRT technology does is rely on the movement of what's called alpha-emitting daughter atoms." "So essentially, we take a biocompatible inert metal seed, which means that if you were to put this seed into the body, there would be no immune effect. Patients could have it inside them for the entirety of their life. Essentially, what we do is we cover this seed with a radiopharmaceutical called Radium-224. We just put Radium-224 on the outside of the seed. Then, we insert it either through a minimally invasive approach or using a different endoscopic approach inside the tumor directly. So now we have the seed covered with the radium inside the tumor, and this is basically where the magic happens."   #AlphaTauMedical #Cancer #TargetedRadiation #ClinicalResearch #RadiationOncology #Oncology #CancerTreatment #AlphaRadiation  alphatau.com Listen to the podcast here

In today's episode, supported by Bristol Myers Squibb, we had the pleasure of speaking with Roxana S. Dronca, MD, about the FDA approval of subcutaneous nivolumab and hyaluronidase-nvhy (Opdivo Qvantig; subcutaneous nivolumab) for advanced or metastatic solid tumors. Dr Dronca is a professor of oncology, a consultant in the Division of Hematology/Oncology in the Department of Internal Medicine, and director of the Mayo Clinic Comprehensive Cancer Center in Jacksonville, Florida. On December 27, 2024, the FDA approved subcutaneous nivolumab across approved adult, solid tumor nivolumab indications, including as monotherapy, monotherapy maintenance after completion of nivolumab in combination with ipilimumab (Yervoy), or in combination with cabozantinib (Cabometyx) or chemotherapy. This regulatory decision was backed by findings from the phase 3 CheckMate-67T trial (NCT04810078) and includes indications for melanoma, renal cell carcinoma, non–small cell lung cancer, urothelial carcinoma, head and neck squamous cell carcinoma, colorectal cancer, esophageal carcinoma, esophageal adenocarcinoma, hepatocellular carcinoma, gastric cancer, and gastroesophageal junction cancer. In our exclusive interview, Dr Dronca discussed the significance of this FDA approval across multiple solid tumor indications, pivotal findings from the CheckMate-67T trial, and how this approval represents a paradigm shift in modern cancer care delivery.

Sonal Gupta, MD, PhD, SVP and Head of Clinical Development at Affyimmune Therapeutics talks with host Emily Walsh Martin, PhD, to explore the challenges of cell therapy clinical trials and how to move patients quickly and thoughtfully through the steps required to receive therapy in aggressive solid tumor cancers.  But first, "we've moved straight from pumpkin spice season into ASGCT Annual Meeting registration season," as Dr. Walsh Martin says. So hop online and join ASGCT, then register and take advantage of the incredible member discounts on Annual Meeting registration. We'll see you in New Orleans, May 13-17, 2025! AnnualMeeting.ASGCT.org/register Music by: https://www.steven-obrien.net/--------------------------Bright New Morning - Steven O'Brien (Used for free under a Creative Commons Attribution 4.0 License: https://creativecommons.org/licenses/by/4.0/)Show your support for ASGCT!: https://asgct.org/membership/donateSee omnystudio.com/listener for privacy information.

In this interview, we sit down with Dr. Hemant Murthy, a professor of medicine in the division of Hematology/Oncology at Mayo Clinic, to explore the groundbreaking potential of CAR T-cell therapy and the crucial role clinical trials play in advancing cancer treatments.Dr. Murthy begins by emphasizing the importance of clinical trials in hematology, reminding us that many of today's standard treatments—like oral medications for chronic myeloid leukemia or advanced therapies for multiple myeloma and acute myeloid leukemia—are the result of past clinical trials. These studies not only push boundaries but also provide a clearer future path for treating diseases.CAR T-cell therapy is a significant part of this evolving landscape. Initially viewed as a last resort for patients with limited life expectancy, CAR T- cell therapy has now become a transformative therapy, with trials showing such strong results that it's being used earlier in treatment regimens, sometimes even before other established procedures like bone marrow transplants. The therapy, which re-engineers a patient's own immune cells to fight cancer, has been particularly effective for conditions such as lymphoma and multiple myeloma. Dr. Murthy explains how this shift in timing and application has dramatically changed patient outcomes, allowing those once facing hospice care to now look forward to longer, more hopeful lives.Dr. Murthy also highlights the meticulous approval process for CAR T- cell therapies. He discusses how several CAR T products, such as axicabtagene ciloleucel and lisocabtagene maraleucel, have been approved for diseases like diffuse large B-cell lymphoma and multiple myeloma due to their success in clinical trials. Importantly, he notes that these treatments are continually evolving, and future trials may yield even better results for more patients.For patients interested in learning about clinical trials, Dr. Murthy stresses the importance of consulting with their oncologists. Trials are essential in driving the next wave of treatments, and they provide an opportunity to explore innovative therapies. He advises patients to ask about trial phases and the logistics involved, such as the number of study visits or the need to stay near treatment centers. Resources like clinicaltrials.gov can also help patients find reputable studies.Looking to the future, Dr. Murthy shares his excitement about emerging therapies, including cellular treatments for solid tumors like melanoma and sarcomas. He talks about innovative approaches like gene editing and the use of different immune cells, such as natural killer cells, to make treatments safer, faster, and more effective. As clinical trials continue to expand, they offer hope for addressing even more cancer types and improving patient care.In closing, Dr. Murthy reflects on how far cancer treatments have come and expresses optimism about the ongoing impact of clinical trials in shaping a brighter future for patients. He encourages patients to ask questions and stay engaged with their healthcare providers to explore all potential treatment options.More:ClinicalTrials.gov: https://clinicaltrials.govMayo Clinic Cancer Center: https://www.mayoclinic.org/departments-centers/cancer-centerThis season is made possible thanks to our sponsors:Kite, a Gilead company: http://www.kitepharma.com/and Bristol Myers Squibb's CAR T support services program:https://www.celltherapy360.com/ Follow the nbmtLINK on Instagram! https://www.instagram.com/nbmtlink/Or visit our website at https://www.nbmtlink.org/

The mini-protein radiopharmaceutical AKY-1189, designed to deliver the alpha-emitting isotope Actinium-225 (225Ac) to tumors expressing the Nectin-4 transmembrane protein, has been found to achieve favorable dosing to tumors, while minimizing exposure to non-target tissues, including the kidney. Data on the biodistribution and tumor uptake of the drug were reported at the 2024 EORTC-NCI-AACR 2024 Molecular Targets and Cancer Therapeutics Symposium held in Barcelona. Researcher Machaba Mike Sathekge, PhD, Professor and Head of the Department of Nuclear Medicine at the University of Pretoria and Steve Biko Academic Hospital in South Africa. He is also CEO of Nuclear Medicine Research Infrastructure and Chairman of the South African Medical Research Council.

Dr. Jeng Her, Founder and CEO of AP Biosciences, is developing T-Cube bispecific antibodies that can target cancer cells and engage T-cells to kill them more effectively and safely than existing treatments. The company is focused on treating hard-to-treat cancers such as HER2-positive breast cancer, lung cancer, head and neck cancer, and pancreatic cancer. The T-Cube bispecific antibodies use CD137 instead of CD3 to activate T-cells, which can lead to better efficacy and safety compared to other T-cell engager antibodies. Jeng explains, "So why not just take two, let's say, monospecific antibodies and then put them together and give them to the patient in the combination therapy? Instead, we wanted to develop bispecific antibodies by fusing two antibodies together into one single molecule. So what's the advantage? Eventually, what it comes down to is the therapeutic window of bispecific antibodies. This means you want your antibodies, your bispecific, to have better efficacy, better safety, and sometimes lower cost of goods since you are only expressing or producing one single drug molecule. So, the way we look at bispecific and the real advantage is not just the additive effect. It's not even the synergistic effect, which means we would like our bispecific antibodies to do something combination therapy cannot do. And that's the value of our bispecific antibodies." "Basically, we have two technology platforms. The first one is an antibody phage display library. We call it Omni-mAb. This library is a live library, which means it has more than 100 billion antibody sequences. That's a collection of the 100 billion sequences. And whatever antigen, whatever conformation of the structure of antigens you have, you could isolate a very high-affinity antibody from the library in probably 4-6 weeks."  #APBiosciences #Antibody #Biotech #Bispecific #ImmunoOncology #Cancer #SolidTumors APBioInc.com Listen to the podcast here

Dr. Jeng Her, Founder and CEO of AP Biosciences, is developing T-Cube bispecific antibodies that can target cancer cells and engage T-cells to kill them more effectively and safely than existing treatments. The company is focused on treating hard-to-treat cancers such as HER2-positive breast cancer, lung cancer, head and neck cancer, and pancreatic cancer. The T-Cube bispecific antibodies use CD137 instead of CD3 to activate T-cells, which can lead to better efficacy and safety compared to other T-cell engager antibodies. Jeng explains, "So why not just take two, let's say, monospecific antibodies and then put them together and give them to the patient in the combination therapy? Instead, we wanted to develop bispecific antibodies by fusing two antibodies together into one single molecule. So what's the advantage? Eventually, what it comes down to is the therapeutic window of bispecific antibodies. This means you want your antibodies, your bispecific, to have better efficacy, better safety, and sometimes lower cost of goods since you are only expressing or producing one single drug molecule. So, the way we look at bispecific and the real advantage is not just the additive effect. It's not even the synergistic effect, which means we would like our bispecific antibodies to do something combination therapy cannot do. And that's the value of our bispecific antibodies." "Basically, we have two technology platforms. The first one is an antibody phage display library. We call it Omni-mAb. This library is a live library, which means it has more than 100 billion antibody sequences. That's a collection of the 100 billion sequences. And whatever antigen, whatever conformation of the structure of antigens you have, you could isolate a very high-affinity antibody from the library in probably 4-6 weeks."  #APBiosciences #Antibody #Biotech #Bispecific #ImmunoOncology #Cancer #SolidTumors APBioInc.com Download the transcript here

In this JCO Precision Oncology Article Insights episode, Mitchell Elliot summarizes the article “Talazoparib in Patients With Solid Tumors With BRCA1/2 Mutation: Results From the Targeted Agent and Profiling Utilization Registry Study” by Dr. Jordan Srkalovic et al.  published on June 12th, 2024. TRANSCRIPT Mitchell Elliott: Hello, welcome to JCO Precision Oncology Article Insights. I'm your host Mitchell Elliott, an ASCO Journals Editorial Fellow. Today I'll be providing a summary of the article titled, “Talazoparib in Patients With Solid Tumors With BRCA1/ 2 Mutation: Results From the Targeted Agent and Profiling Utilization Registry Study,” by Dr. Jordan Srkalovic et al. The Targeted Agent and Profiling Utilization Registry Study is a phase 2 basket trial evaluating the anti-tumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with various solid tumors with germline or somatic BRCA1 and 2 mutations treated with talazoparib are reported. BRCA1 is involved in both non homologous end joining, and homologous recombination, while BRCA2 primarily facilitates homologous recombination. These mutations are present in a range of cancers including breast, ovarian and pancreatic cancers, making them key targets for therapies that inhibit poly (ADP-ribose) polymerase or PARP, a family of proteins critical for DNA repair. PARP inhibitors like talazoparib have shown promise in treating cancers with BRCA mutations as they prevent tumors from repairing DNA damage, thus promoting cell death. Many PARP inhibitors are standard of care in both early and advanced cancers. Talazoparib was previously FDA approved for BRCA related HER2 negative breast cancer and prostate cancer. The TAPUR study aims to investigate the effectiveness of talazoparib and other types of solid tumors with BRCA1 and 2 mutations to expand its potential therapeutic applications. Eligible patients had to meet both general and drug specific criteria for inclusion in the study. General eligibility required participants to have advanced or metastatic solid tumors measurable by the RECIST version 1.1 criteria, a performance status of 0 to 2 based on the Eastern Cooperative Oncology Group Scale, and a genomic target identified through certified laboratory testing. Patients with germline or somatic BRCA1 or 2 mutations were eligible, but the genomic test did not always differentiate between these types of mutations. Additional criteria included being age 18 years or older, using effective contraception and avoiding sperm donation at the set period. Exclusion criteria included patients with HER2 negative breast cancer, prior PARP inhibitor treatments, or certain cardiovascular conditions. The study also excluded patients with recent major surgeries, coagulopathy and serious medical conditions, but there were no criteria related to prior platinum therapies. Patients received 1 milligram of talazoparib daily until disease progression, unacceptable toxicity, or other reasons for discontinuation. The primary endpoint of the study was disease control which was defined by achieving either objective response or stable disease lasting at least 16 weeks as assessed by the RECIST criteria. Secondary endpoints included objective response, progression free survival, overall survival, duration of response, duration of stable disease, and safety. The study enrolled 28 eligible patients with 20 different solid tumors that had BRCA1/2 alterations between December 2019 and September 2021 across 19 clinical sites with most patients, about 89%, enrolled from community-based locations in the United States. The most common tumor type was non-small cell lung cancer accounting for 18% of cases. All patients were included in both the safety and efficacy analyses including three with HER2 negative breast cancer and somatic BRCA alterations. Of the 28 patients, nine had tumors with BRCA1 alterations, 16 had BRCA2 alterations and three had both BRCA1 and BRCA2 alterations. Additionally, 64% of patients had tumors with coalterations and at least one DNA damage repair gene. In the study, one patient achieved a complete response, nine patients had partial response and six patients had stable disease for at least 16 weeks. The overall disease control rate was 57% with an objective response of 36%. The study rejected the null hypothesis of a 15% disease control rate with high statistical significance with a p-value of less than 0.001. The median progression free survival was 24 weeks and median overall survival was 71 weeks. Interestingly, among the 19 patients who received prior platinum-based chemotherapy, 5, or about 26%, had a partial response and 4 had stable disease while on talazoparib. While platinum therapy exposure can be associated with BRCA reversion mutations, it is notable that these patients achieve stable disease with PARP inhibitor treatment. 46% of the 28 patients experienced grade 3 - 5 adverse events or serious adverse events that were possibly related to talazoparib. 14% of patients had possible drug related serious adverse events which included conditions such as anemia, neutropenia, leukopenia, nausea and vomiting. More severe grade 4 or 5 events included anemia, neutropenia, thrombocytopenia, leukopenia, hyponatremia, and increased level of the aspartate aminotransferase and bilirubin. In conclusion, this study demonstrates that talazoparib shows significant antitumor activity in patients with advanced solid tumors carrying both BRCA1 and BRCA2 mutations, even in cancers beyond those for which PARP inhibitors are currently FDA approved. The disease control and objective response rates indicate promising results in heavily pretreated patients who have no standard treatment options left. The findings suggest that PARP inhibitors like telazoparib could be effective in a broad range of cancers, including non-small cell lung cancer, mesothelioma and hepatocellular carcinoma where PARP inhibitors are not yet approved. This could pave the way for expanding the use of these drugs in precision oncology. While talazoparib showed efficacy, the study also reported a notable incidence of grade 3 to 5 adverse events, highlighting the need for careful management of side effects, particularly in heavily pretreated patients. The study calls for further research, particularly in randomized controlled trials to confirm the efficacy of talazoparib in other cancers beyond what is currently approved. It also suggests investigating the effect of DNA damage repair gene alterations and exploring combinations of PARP inhibitors with other targeted therapies. Additionally, further studies are needed to understand the potential differences in response between BRCA1 and BRCA2 mutations. Thank you for listening to JCO Precision Oncology Article Insights and please tune into the next topic. Don't forget to give us a rating and review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at www.asco.org/podcasts. 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.      

We love to hear from our listeners. Send us a message.Carsten Linnemann, Ph.D., CEO of Neogene Therapeutics and Head of Oncology Cell Therapy Clinical Development, AstraZeneca joins Cell & Gene: The Podcast's Erin Harris to discuss T-cell receptor (TCR) therapies for solid cancers. They talk through key challenges and opportunities in developing TCR therapies targeting neoantigens as well as the potential benefits of TCR-T therapies for cancer treatment. Linnemann shares his thoughts on the future landscape of cell therapy in oncology and beyond. Previous episodes of Cell & Gene: The Podcast have focused on TCR therapies, including Episode 50, featuring Affini-T Therapeutics' Co-Founder, CEO, and President Dr. Jak Knowles. Be sure to check out that episode, too. https://www.cellandgene.com/doc/targeting-oncogenic-drivers-for-solid-tumor-cancers-with-affini-t-therapeutics-dr-jak-knowles-0001

Details of the expanding range of cell therapies beyond hematologic malignancy were reported at the 2024 Annual Meeting of the Chinese Society of Clinical Oncology (CSCO) by Oliver Dorigo, MD, PhD, Director of the Division of Gynecologic Oncology at the Stanford Women's Cancer Center in Stanford University. After his talk at CSCO, Dorigo told Oncology Times reporter Peter Goodwin about the promise cell therapies held for improving outcomes in ovarian cancer and other solid tumors, as well as the benefit of the exchange of ideas flowing between China, U.S., and other global players in this young science.

David Mazzo, President and CEO of Lisata Therapeutics, has a lead program focused on metastatic pancreatic ductal adenocarcinoma. The Lisata CendR Platform and drug certepetide efficiently augment the effects of chemotherapy and immunotherapies in the tumor microenvironment. Based on early findings, the future of cancer treatment may involve combining existing therapies with certepetide to personalize treatment for most solid tumors. David explains, "At Lisata, we're developing therapies to combat a challenging problem in the medical field today, which is the effective treatment of solid tumors. Solid tumors are very difficult to treat for two very simple reasons. On the one hand, these tumors generate a layer of cells around them that acts as a physical barrier. It's called the tumor stroma, and it prevents the penetration of many anti-cancer medicines into the tumor, which is why you often don't get the kind of results that one would expect." "The other obstacle these tumors present is that they generate or express a tumor microenvironment that is immunosuppressive, which helps the tumor hide from your innate immune system. It helps it not respond very well to externally administered immunotherapies. When you combine these two challenges, you end up with a set of diseases that remains an enigma in medical science today."   "So our therapy at Lisata called certepetide, our lead product, actually combines the ability to target and penetrate tumors more effectively for co-administered anti-cancer drugs with the ability to modify the tumor microenvironment, making it more immunoreceptive and therefore more likely to respond to your immune system and immunotherapies."  #Lisata #Oncology #Cancer #SolidTumors #Immunotherapies #TumorMicroEnvironment lisata.com Download the transcript here

David Mazzo, President and CEO of Lisata Therapeutics, has a lead program focused on metastatic pancreatic ductal adenocarcinoma. The Lisata CendR Platform and drug certepetide efficiently augment the effects of chemotherapy and immunotherapies in the tumor microenvironment. Based on early findings, the future of cancer treatment may involve combining existing therapies with certepetide to personalize treatment for most solid tumors. David explains, "At Lisata, we're developing therapies to combat a challenging problem in the medical field today, which is the effective treatment of solid tumors. Solid tumors are very difficult to treat for two very simple reasons. On the one hand, these tumors generate a layer of cells around them that acts as a physical barrier. It's called the tumor stroma, and it prevents the penetration of many anti-cancer medicines into the tumor, which is why you often don't get the kind of results that one would expect." "The other obstacle these tumors present is that they generate or express a tumor microenvironment that is immunosuppressive, which helps the tumor hide from your innate immune system. It helps it not respond very well to externally administered immunotherapies. When you combine these two challenges, you end up with a set of diseases that remains an enigma in medical science today."   "So our therapy at Lisata called certepetide, our lead product, actually combines the ability to target and penetrate tumors more effectively for co-administered anti-cancer drugs with the ability to modify the tumor microenvironment, making it more immunoreceptive and therefore more likely to respond to your immune system and immunotherapies."  #Lisata #Oncology #Cancer #SolidTumors #Immunotherapies #TumorMicroEnvironment lisata.com Listen to the podcast here

Listen to a soundcast of the June 13, 2024, and June 21, 2024, Augtyro (repotrectinib) for NTRK gene fusion-positive solid tumors and Krazati (adagrasib) for KRAS G12C-mutated colorectal cancer.

We love to hear from our listeners. Send us a message.KSQ Therapeutics' CSO, Micah Benson, Ph.D., joins Erin Harris to discuss how Tumor-Infiltrating Lymphocytes (TILs) as a treatment modality have the potential to treat a variety of solid tumor types. Benson explains KSQ's Phase 1/2 clinical study, KSQ-001EX, which consists of TILs in which the SOCS1 gene is inactivated by CRISPR/Cas9 gene editing. In addition to solid tumors, Benson also addresses the therapeutic potential for autoimmune disease.

Dr Kummar discusses the significance of targeting TP53 Y220C in solid tumors and early data reported with rezatapopt in TP53 Y220C–mutant solid tumors.

Listen to a soundcast of the April 5, 2024, FDA approval of Enhertu (fam-trastuzumab deruxtecan-nxki) for unresectable or metastatic HER2-positive solid tumors.

·       Nascentmc.com for medical writing assistance for your company.Visit nascentmc.com/podcast for full show notes Cilta-cel for Myeloma: The FDA approved ciltacabtagene autoleucel (Carvykti; cilta-cel) for adults with relapsed or refractory multiple myeloma who have tried at least one prior therapy including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. This CAR T-cell therapy, initially approved in 2022, was confirmed effective in the phase 3 CARTITUDE-4 study, showing significant reduction in disease progression or death risk by 59% compared to standard care. Enhertu for HER2-positive Solid Tumors: Fam-trastuzumab deruxtecan-nxki (Enhertu) received FDA approval for treating unresectable or metastatic HER2-positive solid tumors in adults who have had previous systemic treatment and lack satisfactory alternative options. This therapy, a conjugate of an anti-HER2 antibody and a cytotoxic drug, was first approved in 2019 and targets HER2-expressing cancer cells to potentially minimize damage to normal tissues. Fanapt for Bipolar: Iloperidone (Fanapt) has been approved for the acute treatment of manic or mixed episodes in adults with bipolar I disorder. Previously approved for schizophrenia, iloperidone targets neurotransmitters like dopamine and serotonin. It demonstrated efficacy in a pivotal trial, showing significant improvement on the Young Mania Rating Scale. Zevtera for Multiple Bacterial Infections: Ceftobiprole medocaril sodium (Zevtera) was approved for treating adults with Staphylococcus aureus bloodstream infections, right-sided infective endocarditis, and acute bacterial skin and skin structure infections. Also approved for pediatric community-acquired bacterial pneumonia, ceftobiprole is a broad-spectrum cephalosporin that combats various bacteria including MRSA. TriClip for Tricuspid Regurgitation: The FDA approved the TriClip™ transcatheter edge-to-edge repair system for treating tricuspid regurgitation. This minimally invasive option clips the tricuspid valve leaflets to improve blood flow and prevent the need for surgery. The TRILUMINATE Pivotal trial showed significant improvements in TR severity and quality of life with a good safety profile. Revumenib for Acute Leukemia: The FDA granted priority review to revumenib (SNDX-5613) for treating adult and pediatric patients with relapsed or refractory acute leukemia with KMT2A rearrangements. As a new therapeutic agent, revumenib inhibits the menin-MLL protein interaction crucial in leukemic transformation. Early trial results show promising remission rates, with a PDUFA action date scheduled for September 26, 2024.  

Featuring perspectives from Dr Andrew M Evens and Dr Sonali M Smith, including the following topics:  Introduction: CD3-Based Bispecific Antibodies and the General Medical Oncologist: Lymphomas, Multiple Myeloma … and Solid Tumors? (0:00) Follicular and Mantle Cell Lymphoma (7:17) Diffuse Large B-Cell Lymphoma and Hodgkin Lymphoma (30:10) CME information and select publications   

Hans Hammers discusses trial design and patient selection in the adjuvant setting.

Paul Lammers, M.D., M.Sc., CEO of Triumvira Immunologics joins Cell & Gene: The Podcast to talk to Host Erin Harris about TAC, the company's proprietary T cell Antigen Coupler, which has both autologous and allogeneic approaches. They also discuss targeting relapsed or refractory HER2-positive solid tumors and CLDN18.2-positive solid tumors. And they cover a realistic outlook on the evolution of cancer treatment.