The first wave of CAR-T cell therapy products targeting CD19 showed a curative potential in a subset of patients with lymphoma or leukemia. However, not all patients benefit long term from this therapy—some eventually develop resistance to the CAR-T cells, rendering the therapy ineffective, and others experience cytotoxic effects, rendering the therapy potentially dangerous.

In this talk, Dr. Adrian Bot, VP and Global Head of Translational Medicine and the Head of Research in Santa Monica at Kite, a Gilead Company, shares his insights on the development of Axi-cel, as well as lessons learned about the mechanisms of CAR-T therapy toxicity and resistance. Using reverse translational deep learning in the context of clinical trials and real-world utilization, he defines actionable factors that contribute to efficacy and toxicity, leading to potential treatment optimization and next generation products with increased clinical performance.

Watch the talk to learn more about:

• Evidence from clinical trials for the efficacy and limitations of early-generation CAR-T cell therapies
• The challenges that the tumor immune microenvironment and maintaining product T-cell fitness can impose on CAR-T efficacy
• Strategies for next-generation optimization that preempt or overcome treatment resistance and toxicity

_Presenter:

Adrian Bot, PhD

_{Vice President and Global Head, Translational Medicine and Research Head, Santa Monica @ Kite, a Gilead Company}

_{Adrian Bot, MD, PhD is the Vice President of Translational Sciences at Kite Pharma Inc, a biotechnology company developing genetically engineered T cell therapies, based in Los Angeles, CA. He has more than 20 years of experience in biomedical research and development. Dr. Bot obtained his MD at the University of Medicine and Pharmacy in Timisoara, Romania and his PhD in Biomedical Sciences at Mount Sinai School of Medicine in New York. Subsequently, he was a Guest Scientist at the Scripps Research Institute in La Jolla and Scientist, Principal Scientist and Director of Immunology Research at Alliance Pharmaceutical Corp. in San Diego, CA. In Nov 2002, Dr. Bot joined Allecure Pharmaceuticals which became MannKind Corp, where he was a Director of Research and Development. He had several other appointments at MannKind: Sr. Director of Translational Medicine, Vice President of Scientific Management and Vice President of Research, prior to the appointment as Chief Scientific Officer and then Vice President of Translational Sciences at Kite Pharma Inc. Most currently at Kite Pharma, Dr. Bot has been responsible for overseeing the translational activities in support of the development of Axi-Cel, a novel CAR T cell therapy for B cell malignancies. He has been a long time SITC member and is currently serving on the SITC Industry leadership panel.}

_{Dr. Bot’s background is in theoretical and experimental immunology, cancer research, cell therapies, biomolecules and small molecules spanning all stages of development. He authored or co-authored more than 100 research articles, abstracts, reviews, book chapters and monographs in basic and applied immunology. Dr. Bot is the current Editor in Chief of the International Reviews of Immunology and the Section Editor, Immunology and Immunotherapy of the Journal of Translational Medicine.}