Podcasts about chimeric antigen receptor

Dr Joshua Brody from the Tisch Cancer in New York, Dr Matthew Lunning from the University of Nebraska Medical Center in Omaha and Dr Jason Westin from the University of Texas MD Anderson Cancer Center in Houston discuss chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma and chronic lymphocytic leukemia. Produced by Research To Practice. CME information and select publications here (https://www.researchtopractice.com/SOHO2024/CARTCell/Video).

Interview with Roni Shouval, MD, PhD, author of T-Cell Malignant Neoplasms After Chimeric Antigen Receptor T-Cell Therapy. Hosted by Vivek Subbiah, MD. Related Content: T-Cell Malignant Neoplasms After Chimeric Antigen Receptor T-Cell Therapy

Interview with Roni Shouval, MD, PhD, author of T-Cell Malignant Neoplasms After Chimeric Antigen Receptor T-Cell Therapy. Hosted by Vivek Subbiah, MD. Related Content: T-Cell Malignant Neoplasms After Chimeric Antigen Receptor T-Cell Therapy

On this month's episode we are joined by Dr. Scott McComb, a researcher at the National Research Council of Canada, to talk about Chimeric Antigen Receptor aka CAR T cells! Listen in as we discuss topics such as what exactly is a CAR T cell, how it is currently being used, some current challenges with this therapy, what Dr. McComb brings to the field, and what we are excited to see in the future with CAR T cell therapy! Below are some useful links of things mentioned in the episode: About BioCanRx: https://biocanrx.com/about/about-biocanrx CLIC-01 Trial: https://doi.org/10.3389/fimmu.2022.1074740 Paper mentioned on CAR T cells for autoimmune diseases: https://doi.org/10.1056/NEJMoa2308917 CD22 CAR Paper from Dr. McComb's lab: https://doi.org/10.1016/j.omton.2024.200775 Episode Script: https://drive.google.com/file/d/1h0jUDBnVgdZcZk6aPCJ6IwaCIAt9uRml/view?usp=sharing Don't forget to give us a follow on instagram @wthisimmunotherapy! Or feel free to reach out to us at wthisimmunotherapt@gmail.com Creators & Producers: Gillian Savage, Grace Bernard, and Dr. Pauline Loos  Podcast Logo is designed by Mia Portelance  Music is by Lara Antebi (https://laraantebi.bandcamp.com/)

Welcome to the emDOCs.net podcast! Join us as we review our high-yield posts from our website emDOCs.net. Today on the emDOCs cast, Brit Long, MD (@long_brit) covers Part 1 in a series on complications of CAR T-cell therapy, specifically cytokine release syndrome (CRS). To continue to make this a worthwhile podcast for you to listen to, we appreciate any feedback and comments you may have for us. Please let us know!Subscribe to the podcast on one of the many platforms below:Apple iTunesSpotifyGoogle Play

Michael P. Chu, MD - Chimeric Antigen Receptor T Cells: A New Step in Improving Multiple Myeloma Management

Michael P. Chu, MD - Chimeric Antigen Receptor T Cells: A New Step in Improving Multiple Myeloma Management

Kelsey Nusbaum, MD interviewed by Carlos Garcia, MD

Featuring perspectives from Drs Ajai Chari, Ian Flinn, Nikhil Munshi and Laurie Sehn, including the following topics: Part 1: Case Presentations and Clinical Decision-Making (0:00) Case: A man in his early 70s with diffuse large B-cell lymphoma (DLBCL) arising from follicular lymphoma — Ian W Flinn, MD, PhD (3:46) Case: A man in his late 50s with nongerminal center B-cell-like subtype DLBCL — Laurie H Sehn, MD, MPH (15:57) Case: CAR-T therapy during the pandemic — Nikhil C Munshi, MD (22:16) Case: Anti-BCMC bispecific in triple-class and penta-drug refractory disease — Ajai Chari, MD (33:54) CAR-T therapy for non-Hodgkin lymphoma — Dr Flinn (37:09) Bispecifics for non-Hodgkin lymphoma — Dr Sehn (51:48) CAR-T therapy for multiple myeloma — Dr Munshi (1:13:23) Bispecifics for multiple myeloma — Dr Chari (1:26:14) CME information and select publications

Proceedings from an educational event held in partnership with the 2022 Pan Pacific Lymphoma Conference, featuring perspectives from Drs Ajai Chari, Ian Flinn, Nikhil Munshi and Laurie Sehn, moderated by Dr Neil Love.

Featuring perspectives from Dr Jeremy Abramson and Ms Elizabeth Zerante, including the following topics:  Introduction (0:00) Toxicities with Chimeric Antigen Receptor (CAR) T-Cell Therapy — Grading, Management and Patient Education (10:56) Case: A woman in her early 60s with relapsed/refractory chronic lymphocytic leukemia (CLL) (36:28) Case: A woman in her early 60s with relapsed/refractory CLL/SLL (small lymphocytic lymphoma) (40:46) Case: A man in his early 80s with a history of CLL and double-hit diffuse large B-cell lymphoma (45:15) Clinical Use of CAR T-Cell Therapies for CLL and Lymphomas (55:25) CME information and select publications

A special audio program developed a series of 6 fall webinars held following the 2021 ONS Annual Congress. Featuring perspectives from Dr Jeremy Abramson and Ms Elizabeth Zerante, moderated by Dr Neil Love.

Commentary by Dr. Valentin Fuster

Featuring perspectives from Dr Noopur Raje and Ms Alli McClanahan, including the following topics: Introduction (0:00) Case: A man in his mid-50s with IgA kappa MM — Noopur Raje, MD (12:32) Case: A man in his mid-60s with IgA kappa MM — Alli McClanahan, MSN, APRN, ANP-BC (34:17) Case: A woman in her late 70s with IgA kappa MM and a p53 mutation — Dr Raje (45:03) Case: A man in his late 60s with multiregimen-refractory IgA kappa MM — Ms McClanahan (53:30) NCPD information and select publications

A special audio program developed a series of 11 summer webinars held following the 2021 ONS Annual Congress. Featuring perspectives from Ms Alli McClanahan and Dr Noopur Raje.

A special audio program developed from a series of webinars held in conjunction with the 2021 ASCO Annual Meeting. Featuring perspectives from Drs Caron Jacobson, David G Maloney and Nikhil C Munshi.

A special audio program developed from the eighth in a series of 11 integrated webinars held in association with the 2021 ONS Annual Congress. Featuring perspectives from Ms Sonia Glennie, Ms Alli McClanahan, Ms Elizabeth Zerante and Drs Jeremy Abramson, Caron Jacobson and Noopur Raje.

Proceedings from the last in a series of 11 integrated webinars held in association with the 2021 ONS Annual Congress. Featuring perspectives from Drs Jeremy Abramson, Caron Jacobson and Noopur Raje on cases from the practices of Ms Sonia Glennie, Alli McClanahan and Ms Elizabeth Zerante, including the following topics: Introduction (0:00) CD19-Targeted Chimeric Antigen Receptor (CAR) T-Cell Therapy in Chronic Lymphocytic Leukemia (CLL) and Lymphomas (4:07) Case: A man in his mid-60s with relapsed diffuse large B-cell lymphoma (DLBCL) who received axicabtagene ciloleucel — Sonia Glennie, ARNP, MSN, OCN (5:09) Case: A woman in her early 60s with relapsed CLL who received lisocabtagene maraleucel — Elizabeth Zerante, MS, AGACNP-BC (25:35) Case: A man in his early 60s from the Netherlands with high-grade DLBCL who received axicabtagene ciloleucel — Alli McClanahan, MSN, APRN, ANP-BC (33:28) COVID-19, CAR T-Cell Therapy and Clinical Oncology (47:17) B-Cell Maturation Antigen (BCMA)-Targeted CAR T-Cell Therapy in Multiple Myeloma (1:01:33) Case: A man in his late 60s who received BCMA-targeted CAR T-cell therapy bb21217 – Ms McClanahan (1:08:49) Case: A man in his mid-60s who received BCMA-targeted CAR T-cell therapy bb21217 during the COVID-19 pandemic — Ms McClanahan (1:15:13) The Challenges of Oncology and Hope for the Future: “What Is to Give Light Must Endure the Burning” (1:23:00) NCPD information and select publications

CAR T-cell therapy (Chimeric Antigen Receptor) is a new expensive immunotherapy used in the treatment of various cancers. Due to the high cost ($375,000-$500,000 per dose), it is important to ensure that billing and coding is correct and complete on outpatient claims.

Engineered T cells that hunt and kill blood cancers have recently obtained three landmark FDA approvals, forever changing the way we treat this disease. Even with its massive clinical success, these cells come with life-threatening neurotoxicities. But is neurotoxicity a set feature of using T cell therapies or is our engineering accidentally targeting the brain? Utilizing advances in bioinformatics and the huge sequencing datasets available to science, Kevin uncovers similarities between a cell type in our brain and the cancer we target with engineered cells. Finding this needle in a haystack, Kevin creates a link between how we engineer these cells and the neurotoxicities we see, discovering a potential root cause of the problem and generating a rule for how to engineer around it.About the AuthorKevin recently received his PhD from Stanford University in the labs of Professor Howard Chang and Professor Ansuman Satpathy. These labs specialize in uncovering the molecular mechanisms of disease using advanced sequencing modalities.Bridging both biology and computer science, Kevin’s background and expertise made him uniquely suited to hunt down the culprit of CAR T cell neurotoxicity.Key TakeawaysCAR T cells are excellent at killing blood cancers but are not without side-effects -- they can cause severe neurotoxicities.The receptor engineered into CAR T cells was thought to be specific to these blood cancers, ensuring the therapies don't attack healthy tissue.Kevin looked at publically available single cell sequencing data to find a small subset of brain cells hiding in plain sight that the CAR T cells could attack. In mice, engineered “blood cancer specific” T cells attack the brain, demonstrating that neurotoxicity is an off-target effect of the therapy, not a byproduct.TranslationThe finding points to the potential need for different engineered receptors to be used to target these blood cancers.As CAR T cells expand to other cancers and malignancies, this process can be run to ensure we engineer cells that minimize the opportunity for damage to healthy tissue.First Author: Kevin ParkerPaper: Single-Cell Analyses Identify Brain Mural Cells Expressing CD19 as Potential Off-Tumor Targets for CAR-T Immunotherapies

Hundreds of iterations of immune cells that are engineered to kill cancer have already been designed. Corina reached outside of this box to use the same synthetic biology principles to engineer T cells to attack senescent cells, a cell type that contributes to diseases of aging.  Corina walks us through how her engineered T cells know the difference between a diseased cell and healthy tissue, how she stumbled upon the chimeric antigen receptor that made this possible, and how these new T cells are being moved from academia to the clinic.About the AuthorCorina is a physician scientist who performed this work under Professor Scott Lowe at Memorial Sloan Kettering in New York City. Dr. Lowe and his team are world experts in dissecting how functional changes in a cell make them go from healthy to cancerous.Corina became fascinated with translation biotechnology after seeing her mother survive a life threatening disease using a new therapy in a clinical trial.Key TakeawaysT cells are the part of the immune system that have the ability to target and kill other cells in the body in a way similar to drug sniffing dogs.Using the hottest tool in synthetic immunology, the chimeric antigen receptor (CAR), T cells can be engineered to target and attack almost anything we like.A major hurdle to engineering these cells is finding something to target that is overrepresented in disease cells and virtually absent in healthy cells.When targeted to senescent cells, these T cells can kill precancerous cells and reverse diseases related to aging and poor diet.TranslationCorina’s research contains excellent demonstrations of these cells working in preclinical models -- mice that mimic human diseases.To move to human trials, Corina must update the therapy to attack human versions of the cells and begin to work toward understanding its safety and efficacy.Corina believes the best people to take on this challenge are the researchers who have intimate knowledge of the method and who care deeply about the disease it could cure.First Author: Corina Amor VegasPaper: Senolytic CAR T cells reverse senescence-associated pathologies. Nature, 2020.Follow Fifty Years on Twitter!If you’re an author of an upcoming paper in bio or know of any interesting papers dropping soon and want to hear from the authors, drop us an email at translation [AT] fifty [DOT] vc.

Oncology Grand Rounds Series: Part 9 — Faculty Presentation 3: Ms Zerante on the following topics: Case (Ms Zerante): A woman in her early 40s with ALL Case (Ms Zerante): A woman in her early 70s with diffuse large B-cell lymphoma (DLBCL)  Case (Ms Zerante): A man in his late 70s with DLBCL CNE information and select publications

Oncology Grand Rounds Series: Part 9 — Faculty Presentation 5: Dr Richards on the following topics: Case (Dr Richards): A woman in her late 50s with MM Case (Dr Richards): A man in his early 60s with MM CNE information and select publications

Oncology Grand Rounds Series: Part 9 — Faculty Presentation 4: CAR T-cell therapy for multiple myeloma (MM) — Dr Munshi CNE information and select publications

Oncology Grand Rounds Series: Part 9 — Faculty Presentation 2: CAR T-cell therapy for acute lymphoblastic leukemia (ALL) — Dr Komanduri CNE information and select publications

Oncology Grand Rounds Series: Part 9 — Chimeric antigen receptor (CAR) T-cell therapy for aggressive and indolent B-cell lymphomas — Dr Neelapu CNE information and select publications

Featuring a discussion on recent clinical trial data on the use of CAR T-cell therapy in the management of non-Hodgkin lymphoma with Dr Tanya Siddiqi, moderated by Neil Love, MD.

For this special edition of Oncology Today, I met with Dr Tanya Siddiqi from the City of Hope National Medical Center in Duarte, California, to discuss recently published and emerging research in the use of chimeric antigen receptor T-cell therapy for patients with non-Hodgkin lymphoma. CME information and select publications here (http://www.researchtopractice.com/OncologyTodayCARTNHL20).

Featuring a discussion on recent clinical trial data on the use of CAR T-cell therapy in the management of non-Hodgkin lymphoma with Dr Tanya Siddiqi, including the following topics: CAR T-Cell Therapy in B-Cell Non-Hodgkin Lymphoma — Tanya Siddiqi, MD (00:00) Case: A man in his late 50s with recurrent DLBCL attains complete remission after receiving axicabtagene ciloleucel on the Phase I/II ZUMA-1 trial (32:19) Case: A woman in her mid-60s with relapsed/refractory DLBCL receives lisocabtagene maraleucel on the Phase I TRANSCEND NHL 001 study (36:07) Case: A man in his late 60s with multiple regimen-relapsed CLL receives lisocabtagene maraleucel on the Phase I/II TRANSCEND CLL 004 study (38:34) Tumor lysis syndrome in patients receiving CAR T-cell therapy; FDA regenerative medicine advanced therapy designation for tisagenlecleucel in relapsed/refractory follicular lymphoma (43:08) CME information and select publications

Dr. Stephen Hunger is a Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. In today's ASCO eLearning Podcast, Dr. Hunger will discuss two patient cases related to CAR T-cell therapy. While the two cases are similar, the recommended treatments can be different. We hope you enjoy this episode. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts or Google Play. We truly value your feedback, so please leave a review. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org.   Transcription:  The purpose of this podcast is to educate and inform. This is not a substitute for 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hi, my name is Stephen Hunger. I'm a professor of pediatrics in the Perelman School of Medicine at the University of Pennsylvania, and chief of the Division of Oncology and director of the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia. My career has focused on clinical, translational, and basic research regarding childhood Acute Lymphoblastic Leukemia, or ALL. One of the most exciting recent advances in cancer medicine is the development of Chimeric Antigen Receptor-redirected, or CAR-T cell therapy for relapsed in refractory pediatric B cell ALL. Today, I will present two cases that have similarities, but also important differences that highlight key questions and uncertainties regarding when and how to use CAR T cells in pediatric ALL. Currently the only CAR T cell product FDA approved for treatment of children and young adults up to age 25 with relapsed refractory ALL is tisagenlecleucel, trade name Kymriah. Additional CAR T cell products are in the late stages of testing, and will likely become FDA approved soon. My discussion today will focus on tisagenlecleucel, which can persist for years following therapy. Indeed, the first child treated at CHOP for ALL with CAR T cells in 2012 still has detectable CAR T cells over eight years later. Our first patient is Sue, who is currently 15 years old and has B-ALL that relapsed for the second time. She was first diagnosed at age 7, at which time she had an 80,000 white blood cell count. She was treated with standard chemotherapy with an excellent response, but relapsed during maintenance therapy 22 months following her diagnosis. Because this relapse occurred on therapy, she was considered high risk, and allogeneic transplant was considered the therapy of choice. She entered a second remission and became MRD negative after two cycles of consolidation therapy. Her brother was HLA identical, and she underwent a matched sibling transplant in MRD negative second remission following a cyclophosphamide mind plus total body radiation preparative regimen. She engrafted rapidly, had no GBHD, and was weaned off immunosuppression by six months post-transplant. One year post-transplant, she presented with bone pain and was found to have a second bone marrow relapse of B-ALL. Her leukemia cells were CD19 positive. Our second patient is 15-year-old Damian, who was diagnosed with CD19 positive B cell ALL four months ago. His initial white blood cell count was 80,000, and the cytogenetic and molecular studies did not show any known high or low-risk features or targetable lesions. He was treated with standard chemotherapy, but did not enter remission with 50% blasts at the end of four weeks of induction therapy. He received one month of consolidation chemotherapy with a Children's Oncology Group augmented BFM regimen, but still had 35% blasts after that therapy. He then received a four-week course of the CD3/CD19 BiTE blinatumomab, but again had 30% blasts at the end of that therapy. The blasts remained strongly CD19 positive. His 17-year-old sister is fully HLA matched. Both of these patients have relapsed refractory ALL, and meet the FDA approved indication for tisagenlecleucel, which is patients up to 25 years of age with B cell precursor ALL that is refractory or in second or later relapse. Sue is in her second relapse, and thus qualifies. Refractory is not defined precisely in the indication, but I think all would classify Damian as having refractory ALL, given that he has failed to enter remission with three different regimens. The pivotal trial that led to the approval of tisagenlecleucel was called ELIANA, and the results were published in the New England Journal of Medicine in 2018, with my colleague Shannon Maude being the first author. Of note, that study prohibited patients who had received prior CD19-directed therapy, so Damian would not have been eligible to enroll. However, the FDA label does not mention this, and many patients have been treated with tisagenlecleucel following earlier blinatumomab therapy. Thus, Sue and Damian are good candidates for tisagenlecleucel. Both are also medically in good condition without active infection or end organ dysfunction. There are also important differences between Sue and Damien. Sue has relapsed post-transplant while Damien has an HLA-matched sibling, but has never undergone transplant because he has never entered remission. Transplant with high level marrow disease, as he has currently, 30% blasts, is generally viewed futile, and the best transplant outcomes occur when patients are MRD negative immediately pre-transplant. A key current question in therapy of relapsed refractory ALL is whether CAR T cells should be used as a definitive therapy with responders receiving no subsequent antileukemia treatment, or as a so-called bridge to transplant, a means to get patients to an MRD negative state so that they can then undergo transplant as definitive therapy. There is no current definitive answer to this question, and these two cases help to highlight the issues to consider. Both Sue and Damian undergo T cell apheresis with a good collection. Cells are sent to the manufacturer to make the CAR T cells, a process that takes about four weeks. They receive low-intensity maintenance therapy for two weeks with adequate disease control, and then no therapy is given for two weeks. Both have adequate manufacture of CAR T cells, and then receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by CAR T cell infusion. Both patients have mild signs of cytokine release syndrome not requiring intervention. At day 30 post-infusion, both Sue and Damian are in an MRD negative complete remission and have no detectable circulating B cells. What should happen next? While some feel that the long-term efficacy of CAR T cells have not yet been established, and that transplant should be used as a consolidative therapy in almost all cases, many others believe that a long-lasting CAR T cell product such as tisagenlecleucel can be used as definitive therapy in some cases. In the initial ELIANA publication, 81% of the 75 relapsed refractory ALL patients infused with tisagenlecleucel obtained in MRD negative complete remission within three months, usually after one month. And the 12-month event-free survival and overall survival rates were 50% and 76%. More mature survival data from ELIANA shows a two-year relapse-free survival rate of 61% among those achieving remission. Like Sue and Damian, the patients in this trial were heavily pretreated with a median of three prior regimens and 61% had previously undergone transplant. Knowing that many patients can survive long term with no further therapy post-CAR T cell infusion, there is limited enthusiasm for a second transplant among physicians, patients, or their parents if a good response is obtained and maintained. So for Sue, I would recommend close monitoring, but no additional therapy as long as she showed continued evidence of response for 6 to 12 months. I would repeat bone marrow MRD testing at 60 and 90 days and every three months thereafter, and measure peripheral blood B cell numbers monthly for at least six months. B cell depletion is a good surrogate for CAR T cell activity, as normal CD19 positive cells are also killed. If Sue remains MRD negative and has no circulating CD19 positive B cells for at least six months, then there is a good hope that no more therapy is needed. Damian is a more complicated case, as he has never undergone transplant and has an HLA-identical donor, and now has excellent disease control and is in good medical condition to undergo a transplant. There are short-term risks of transplant with a 100-day mortality risk of 5% to 10% for a teenager. And there are also long-term risks related to the transplant procedure and/or graft versus host disease. The long-term risks of tisagenlecleucel appear limited other than the persistent B cell depletion, but the longest followup is only eight years, and few patients have more than five years of followup. So we have no idea about the efficacy and potential risks 10 to 20 or more years post-infusion. Damian failed three induction attempts. If his leukemia comes back, one may never be able to get him back into a healthy MRD negative remission. So there is a good argument that his best chance for definitive therapy is with transplant. Given this, many would strongly recommend transplant as consolidative chemotherapy for Damian. However, it's also possible that Damian has now received curative therapy and will never relapse. Highlighting the uncertainty surrounding this question, our group at CHOP, which has treated over 300 patients with relapsed refractory ALL with CAR T cells, does not have a clear consensus on what to do for patients like Damian. It's our practice to summarize the potential advantages and disadvantages of transplant versus no further therapy, and help the patient and their family decide what is the best course for them. To summarize, tisagenlecleucel is an exciting therapy that provides new opportunities for children and young adults with relapsed and refractory ALL. However, the field of cellular immunotherapy is young, and there are many uncertainties, particularly surrounding the issue of definitive therapy versus bridge to transplant. Today, we lack the followup data needed to make definitive statements, and patients and families need to understand that and be full partners in these complicated decisions. Thank you very much for listening. Thank you for listening to this week's episode of the ASCO eLearning weekly podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive eLearning center at elearning.asco.org.

Featuring an interview with Dr Nikhil Munshi about recently published and emerging research on the use of CAR T-cell therapy in multiple myeloma, including the following topics: Chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma (MM) — Nikhil C Munshi, MD (00:00) Case: A woman in her mid-60s with relapsed/refractory (R/R) IgG kappa MM treated with anti-BCMA CAR T-cell therapy (20:31) Case: A man in his early 60s with R/R MM with adverse cytogenetics (25:58) Case: A man in his late 70s with R/R IgG kappa MM who responds to re-treatment with CAR T-cell therapy (29:52) Future directions in anti-BCMA CAR T-cell therapies for MM; steps toward liberalizing eligibility criteria (33:08)   CME information and select publications

For this special edition of Oncology Today, I met with Dr Nikhil Munshi from the Dana-Farber Cancer Institute in Boston to discuss recently published and emerging research on the use of CAR T-cell therapy in multiple myeloma.

A special audio program developed from the ninth in a series of 11 integrated webinars held in association with the 2020 ONS Annual Congress. Featuring perspectives from Dr Krishna Komanduri, Dr Nikhil C Munshi, Dr Sattva S Neelapu, Dr Tiffany Richards and Ms Elizabeth Zerante.

Proceedings from the ninth in a series of 11 integrated webinars held in association with the 2020 ONS Annual Congress. Featuring perspectives from Dr Krishna Komanduri, Dr Nikhil C Munshi, Dr Sattva S Neelapu, Dr Tiffany Richards and Ms Elizabeth Zerante on the following topics: Introduction (00:00) Overview of Chimeric Antigen Receptor (CAR) T-Cell Therapy (01:07) Side Effects Associated with CAR T-Cell Therapy (22:30) Anti-BCMA CAR T-Cell Therapy in Multiple Myeloma (41:02) CD19-Directed CAR T-Cell Therapy for Aggressive Lymphomas (01:01:37) CAR T-Cell Therapy in Acute Lymphoblastic Leukemia (01:14:57) CNE information and select publications

Commentary by Dr. Anju Nohria

Commentary by Dr. Valentin Fuster

Commentary by Dr. Valentin Fuster

Proceedings from the First Annual Miami General Medical Oncology Symposium — Keynote Lecture: Featuring perspectives from Drs David L Porter, Jonathan L Kaufman and Sattva S Neelapu on chimeric antigen receptor (CAR) T-cell therapy. Introduction — Dr Neil Love (00:00) Keynote Address: CAR T-Cell Therapy and the General Medical Oncologist — Dr Porter (2:49) Targeting the Immune System in Myeloma: New CAR T Cells — Dr Kaufman (1:04:38) CAR T-Cell Therapy for B-Cell Lymphomas — Dr Neelapu (1:23:16) Select publications

Medicine Grand Rounds March 22, 2019 John M. Hill, MD Associate Professor of Medicine Geisel School of Medicine Director, Allogeneic Blood and Marrow Transplant Program Norris Cotton Cancer Center Dartmouth-Hitchcock Medical Center

Dr. Carl June is the director of the Center for Cellular Immunotherapies at the University of Pennsylvania Perelman School of Medicine. Stephen Morrissey, the interviewer, is the Managing Editor of the Journal. C.H. June and M. Sadelain. Chimeric Antigen Receptor Therapy. N Engl J Med 2018;379:64-73.

Host: Shira Johnson, MD Guest: Robert Vonderheide, MD For years, the foundations of cancer treatment, surgery, chemotherapy, and radiation therapy were utilized with the objective of weakening cancer. But over the past several years, immunotherapy – therapies that enlist and strengthen the power of a patient’s immune system to attack tumors - has emerged as a new tool for fighting cancer. In August 2017, one such treatment approach, called Chimeric Antigen Receptor or CAR T-cell Therapy, received FDA approval for the treatment of children and young adults with acute lymphoblastic leukemia (ALL). Additionally, research is continuing to look at CAR-T therapy’s effectiveness for treating solid tumors as well. Host Dr. Shira Johnson sits down with Dr. Robert Vonderheide, Director of the Abramson Cancer Center of the University of Pennsylvania and the John H. Glick, MD, Abramson Cancer Center Director’s Professor, to talk about the potential of CAR-T therapy alongside other emerging immunotherapies in fighting cancer.

Host: Shira Johnson, MD Guest: Robert Vonderheide, MD For years, the foundations of cancer treatment, surgery, chemotherapy, and radiation therapy were utilized with the objective of weakening cancer. But over the past several years, immunotherapy – therapies that enlist and strengthen the power of a patient’s immune system to attack tumors - has emerged as a new tool for fighting cancer. In August 2017, one such treatment approach, called Chimeric Antigen Receptor or CAR T-cell Therapy, received FDA approval for the treatment of children and young adults with acute lymphoblastic leukemia (ALL). Additionally, research is continuing to look at CAR-T therapy’s effectiveness for treating solid tumors as well. Host Dr. Shira Johnson sits down with Dr. Robert Vonderheide, Director of the Abramson Cancer Center of the University of Pennsylvania and the John H. Glick, MD, Abramson Cancer Center Director’s Professor, to talk about the potential of CAR-T therapy alongside other emerging immunotherapies in fighting cancer.

Host: Shira Johnson, MD Guest: Robert Vonderheide, MD For years, the foundations of cancer treatment, surgery, chemotherapy, and radiation therapy were utilized with the objective of weakening cancer. But over the past several years, immunotherapy – therapies that enlist and strengthen the power of a patient’s immune system to attack tumors - has emerged as a new tool for fighting cancer. In August 2017, one such treatment approach, called Chimeric Antigen Receptor or CAR T-cell Therapy, received FDA approval for the treatment of children and young adults with acute lymphoblastic leukemia (ALL). Additionally, research is continuing to look at CAR-T therapy’s effectiveness for treating solid tumors as well. Host Dr. Shira Johnson sits down with Dr. Robert Vonderheide, Director of the Abramson Cancer Center of the University of Pennsylvania and the John H. Glick, MD, Abramson Cancer Center Director’s Professor, to talk about the potential of CAR-T therapy alongside other emerging immunotherapies in fighting cancer.

Host: Shira Johnson, MD Guest: Robert Vonderheide, MD For years, the foundations of cancer treatment, surgery, chemotherapy, and radiation therapy were utilized with the objective of weakening cancer. But over the past several years, immunotherapy – therapies that enlist and strengthen the power of a patient’s immune system to attack tumors - has emerged as a new tool for fighting cancer. In August 2017, one such treatment approach, called Chimeric Antigen Receptor or CAR T-cell Therapy, received FDA approval for the treatment of children and young adults with acute lymphoblastic leukemia (ALL). Additionally, research is continuing to look at CAR-T therapy’s effectiveness for treating solid tumors as well. Host Dr. Shira Johnson sits down with Dr. Robert Vonderheide, Director of the Abramson Cancer Center of the University of Pennsylvania and the John H. Glick, MD, Abramson Cancer Center Director’s Professor, to talk about the potential of CAR-T therapy alongside other emerging immunotherapies in fighting cancer.

Host: Shira Johnson, MD Guest: Robert Vonderheide, MD For years, the foundations of cancer treatment, surgery, chemotherapy, and radiation therapy were utilized with the objective of weakening cancer. But over the past several years, immunotherapy – therapies that enlist and strengthen the power of a patient’s immune system to attack tumors - has emerged as a new tool for fighting cancer. In August 2017, one such treatment approach, called Chimeric Antigen Receptor or CAR T-cell Therapy, received FDA approval for the treatment of children and young adults with acute lymphoblastic leukemia (ALL). Additionally, research is continuing to look at CAR-T therapy’s effectiveness for treating solid tumors as well. Host Dr. Shira Johnson sits down with Dr. Robert Vonderheide, Director of the Abramson Cancer Center of the University of Pennsylvania and the John H. Glick, MD, Abramson Cancer Center Director’s Professor, to talk about the potential of CAR-T therapy alongside other emerging immunotherapies in fighting cancer.

Host: Shira Johnson, MD Guest: Robert Vonderheide, MD For years, the foundations of cancer treatment, surgery, chemotherapy, and radiation therapy were utilized with the objective of weakening cancer. But over the past several years, immunotherapy – therapies that enlist and strengthen the power of a patient’s immune system to attack tumors - has emerged as a new tool for fighting cancer. In August 2017, one such treatment approach, called Chimeric Antigen Receptor or CAR T-cell Therapy, received FDA approval for the treatment of children and young adults with acute lymphoblastic leukemia (ALL). Additionally, research is continuing to look at CAR-T therapy’s effectiveness for treating solid tumors as well. Host Dr. Shira Johnson sits down with Dr. Robert Vonderheide, Director of the Abramson Cancer Center of the University of Pennsylvania and the John H. Glick, MD, Abramson Cancer Center Director’s Professor, to talk about the potential of CAR-T therapy alongside other emerging immunotherapies in fighting cancer.

Coming up on Biotechnology Focus Radio : The future of made-in-Canada CAR-T cells looks bright, Roche Canada and Merck each launch their own individual collaborative cancer research initiatives, and using immunotherapies to kill brain cancer Welcome to another episode of Biotechnology Focus Radio. I’m your host Shawn Lawrence, here to give you a rundown of this week’s top stories on the Canadian biotech scene. As you can tell by our teaser intro, cancer research and new initiatives into new therapies to tackle the disease figure prominently in our news headlines this week, and this is not a coincidence as February happens to be National Cancer Prevention Awareness Month. Story 1 On that note, our first story takes us to Ottawa, ON, where a team of researchers at the Children’s Hospital of Eastern Ontario (CHEO) have made a discovery, featured in Nature, center around a promising combination of immunotherapies that are able to deliver a one-two punch to brain cancer tumours in mice.  Led by Dr. Robert Korneluk, distinguished professor at the University of Ottawa and senior scientist at the CHEO Research Institute, the Ottawa reseach team was able to show in mice that a combination of drugs known as SMAC Mimetics and immune checkpoint inhibitors (ICIs) amplifies kill rates of cancer tumour cells in laboratory testing. The research team also discovered a new mechanism by which the combination promotes long-term immunity against glioblastoma tumours. The combination therapy also proved to be highly effective against breast cancer and multiple myeloma. According to Dr. Korneluk, these findings represent a significant evolution in the field of immunotherapy, for the first time showing the synergistic tumour-killing impact of combining SMAC Mimetics with immune checkpoint inhibitors for glioblastoma. As part of this latest project SMAC Mimetics known as LCL161 and Birinapant were combined with ICI antibodies targeting PD-1 and CTLA-4 immune checkpoints. The findings have their roots in research conducted back in 2014, when a team of scientists led by Dr. Korneluk discovered that combining SMAC Mimetics with immune stimulators or live virus therapies had a synergistic or amplified tumour-killing effect that was greater than either agent on its own. Today’s news shows that SMAC Mimetics also have a powerful synergistic effect with ICIs, relatively new drugs that are showing great promise in the clinic. Eric Lacasse, a scientist at the CHEO Research Institute, adds that two drug companies have initiated human clinical trials this year to assess the impact of this combination of SMAC Mimetics and ICIs on patients with a variety of cancers. Although it could be years before any clinical trials begin for adults or children with the deadly brain cancer, glioblastoma, we’re looking forward to seeing how scientific evidence from these experimental treatments adds to our knowledge. It’s an exciting, exploratory field and we hope we’ve hit a home run.” Shawn Beug was the lead author of both the 2014 and 2017 papers, and the research was funded by the Canadian Cancer Society Research Institute, Brain Canada (with financial support from Health Canada through the Canada Brain Research Fund) and the Canadian Institutes of Health Research. In addition, the work was supported by donations to the Ottawa Regional Cancer Foundation, the Kiwanis Medical Foundation and the CHEO Foundation. Story 2 Continuing with the Cancer Research theme, Hoffmann-La Roche Limited (Roche Canada) reports that Toronto’s Princess Margaret Cancer Centre has joined the company's global cancer immunotherapy Centres of Research Excellence (imCORE) Network. The network brings together the world's leading scientific and clinical experts in cancer immunotherapy to collaborate on the investigation and development of promising new treatment approaches for the disease. As part of gaining a better understanding immune biology and cancer, and to ultimately improve treatment options, this includes initiating pre-clinical and clinical research based on the latest scientific discoveries in cancer immunotherapy and to aggregate, as well as share data within the Network to help accelerate research for people living with cancer.  The imCORE Network is comprised of 21 academic centres, inclusive of Princess Margaret Cancer Centre, from nine countries across the globe.   Dr. Lillian Siu, medical oncologist at Princess Margaret Cancer Centre and Site Lead for the imCORE Network explains why the imCORE newtwork is exciting in the follow audio clip. http://stream1.newswire.ca/media/2017/02/14/20170214_C8704_VIDEO_EN_881863.mp4 As a part of a global announcement regarding the launch of the imCORE Network, Roche has also made a commitment to invest up to 100 million Swiss Francs (more than $130 million Canadian dollars) to support basic and clinical research collaborations related to cancer immunotherapy. Story 3 In an exciting public/private partnership, stakeholders in Quebec have launched a new research, development and investment hub to help accelerate the fight against cancer. The hub, called Oncopole is backed by a $15-million investment by Merck that will be administered over three years and overseen by the Fonds de recherche du Québec – Santé (FRQS). Through its model, Oncopole brings together various stakeholders under one flagship hub in oncology. It’s conception was structured with the involvement of more than 50 experts from the scientific community over the past year, who helped to identify its priorities. Recognizing the range of resources and infrastructures currently available as well as the strategic positioning of many researchers in Québec, the Hub will aspire to strengthen the research and innovation ecosystem in the province. Some functions of Oncopole will include enabling the incubation and creation of companies that will capitalize on innovation; and positioning cancer care in Québec among the best in the world in terms of clinical outcome, patient experience and system efficiency. Based on a thorough analysis of the various hosting possibilities identified across Québec, the Institute for Research in Immunology and Cancer (IRIC) of the Université de Montréal was selected as the establishment which will host the Oncopole’s coordinating offices. Additionally, the FRQS and Merck hope that this initial investment will attract other partners to join the Oncopole and make it a truly collaborative initiative. Story 4     Switching gears to the bioindustrial sector, the Biotechnology Innovation Organization (BIO) announces that registration and housing are now open for the 2017 World Congress on Industrial Biotechnology. The conference, now in its 14th year brings brings together from across the globe business leaders, investors, academics and policymakers in the biofuels, biobased products, renewable chemicals, synthetic biology, food ingredients and biomass sectors. Industrial and environmental biotechnology is at the forefront of the biobased economy, generating good-paying jobs and making cleaner products and processes. This year event will be held July 23-26, 2017 at the Palais des congrès de Montréal in Montréal, Canada. According to Brent Erickson, executive vice president, Industrial and Environmental at BIO, two new tracks-Flavors, Fragrances and Food Ingredients and Agricultural Crop Technologies and Biomass Supply-have been added to this year’s programming, representing the extended value chain of industrial biotechnology. He adds that the decision to bring the World Congress back to Montréal had very much to do with the success of past events, and the local industries continues support of what has grown into the world’s largest industrial biotechnology conference. In 2016, the BIO World Congress on Industrial Biotechnology drew around 907 industry leaders from 529 companies, 32 countries and 31 states, as well as the District of Columbia and hosted a record 1,961 partnering meetings. For more information on the conference visit http://www.bio.org/worldcongress. Story 4 In our final story this week, BioCanRx, and its partners, are investing $11 million to support 16 collaborative research projects in novel therapies to cure cancer. including research aimed at developing Canada’s clinical Chimeric Antigen Receptor modified T cell (CAR-T) manufacturing capabilities. Considered a powerful new tool in the fight against cancer, CAR-T is on the cutting edge of cancer therapeutics, showing promise in paediatric and adult patients with certain blood cancers such as acute lymphoblastic leukemia and lymphoma. While promising, the development of such therapies require sophisticated manufacturing and expertise. Canada currently does have the basic laboratory infrastructure in place, and with this funding could take significant steps towards fully developing the expertise and capacity required to deliver this technology. The BioCanRx investment is going to research projects that will advance several innovative engineered T cell designs, to accelerate delivery of these novel concepts into clinical testing in Canada. Dr. John Bell, Scientific Director, BioCanRx adds his CAR-T manufacturing initiative is unique in that it represents the Canadian academic community recognizing a gap and stepping up to drive Canadian solutions to meet grassroots efforts taking place in the U.S., China and Europe. He discusses CAR-T cell manufacturing in Canada in the following audio provided by BioCanRX: https://biocanrx.com/wp-content/uploads/custom%20images/BioCanRx_Dr_JohnBellCART3.mp4 To help ensure CAR-T cell therapy is brought to patients safely and effectively, BioCanRx is funding a companion Clinical, Social, and Economic Impact project. It will review the existing base of knowledge and involve patient consultation to design a rigorous CAR-T clinical trial protocol ready to implement once the products are ready for a phase 1 clinical trial. Dr. Manoj Lalu, associate scientist, assistant professor, Clinical Epidemiology and Regenerative Medicine Programs, Ottawa Hospital Research Institute, The Ottawa Hospital and Department of Anesthesiology and Pain Medicine, University of Ottawa discusses CAR-T therapy clinical trial design in the following audio clip. https://biocanrx.com/wp-content/uploads/custom%20images/Dr.%20Lalu%20-%20BioCanRx.mp4 To access the full list of the 16 projects funded, be sure to visit https://biocanrx.com/project-dashboards.   Well that wraps up another episode of the Biotechnology Focus Podcast. We hope you enjoyed it. Be sure to let us know what you think, and we’re also always looking for story ideas and suggestions for future shows, and of course we’d love to hear from you as well, simply reach out to us via twitter @biotechfocus, or by email at the following email address  press@promotivemedia.ca. And remember, you can also listen to past episodes online via our podcast portal at www.biotechnologyfocus.ca . For all of us here at Biotechnology Focus, thanks for listening.

Dr. Stephen A. Grupp talks to ecancer at the 2013 ASH Annual Meeting in New Orleans about results from a group of cell therapy trials using the chimeric antigen receptor (CAR) cell engineering approach to manipulate the T cells of 22 children and five adults with relapsed, treatment-resistant acute lymphocytic leukaemia. After treatment with their own cells re-engineered to seek, attack, and kill leukaemic cells, 24 patients (19 children, five adults) achieved a complete response.