Deciphering CAR-T Cells: Exploring Functional Mechanisms to Drive Next Generation Immunotherapy

Participating experts: Stanley Riddell, MD (UCSF), and Wendell Lim, PhD (Fred Hutchison Cancer Research Center)
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Explore free signaling pathways relevant to immuno-oncology:
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Chimeric antigen receptor (CAR) T-cell immunotherapy shows great promise as a treatment for cancer and other diseases. CAR T cells are patient-derived T cells engineered to express an antigen receptor that is specific for the patient’s tumor cells. While there has been some clinical success with CAR-T therapy, researchers still face challenges in optimizing its effectiveness, for example when applying it to solid tumors, and in addressing safety concerns such as neurotoxicities. Understanding the functional mechanisms and underlying signaling pathways of CAR T cell activity is crucial to overcoming these challenges. Intensive efforts have been made in recent years to decipher these mechanisms and to elucidate unique signaling pathways in different T-cell subpopulations, in order to develop better clinical strategies. This webinar will introduce the audience to the range of different T-cell populations and the roles they play in normal immune function as well as disease, and will explain how recent breakthroughs in our understanding of these specialized immune cells can lead to improvements in disease treatment.

Table of Contents:
0:08 Welcome and overview
3:00 Stanley Riddell speaker profile
3:35 Role of CAR signaling domains for instructing T cell function and fate
4:17 TCR and costimulatory receptor engagement induce cell responses through phosphoprotein signaling
6:04 CAR-T cells with CD28/ζ or 4-1BB/ζ costimulatory domains behave differently
9:58 CD28/CD3ζ and 4-1BB/CD3ζ CAR stimulation comparison
16:40 Tuning CAR signaling
19:00 Conclusions: CD28/CD3ζ and 4-1BB/CD3ζ CAR
20:13 Wendell Lim speaker profile
20:59 Laying the foundation for robust next-gen CAR T Cell Therapies: What are the critical building blocks?
21:47 CAR (Chimeric antigen receptor) overview animation
22:23 Current CAR therapies: pros and cons and the “Hype Cycle”
25:59 Improving anti-cancer T cell therapy – needs and challenges
28:55 Case study: CD19 CAR
31:10 How to harness the full power of living therapies
33:17 Challenge of solid tumor recognition
35:50 Combinatorial antigen recognition, multi-receptor integration
37:00 Beyond CARs: new platforms for cell-cell recognition: SynNotch
40:37 Combinatorial antigen recognition animation: design and animal model
42:36 Multi-antigen tumor discrimination: Results
44:10 Future pipeline for designing cell therapies
48:54 Questions and Answers

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