Learning from patient data to advance engineered T cell immunotherapy designs
Zinaida Good, PhD
Assistant Professor, Division of Immunology and Rheumatology, Center for Biomedical Informatics Research, Dept. of Medicine, Stanford University Dr. Good's work is focused on investigating why chimeric antigen receptor (CAR) T cell immunotherapies succeed or fail in patients .
Friday, January 17, 2025
11:00am - 12:00pm
James H. Clark Center, Room S360, 3rd floor next to the Coffee Shop
Zoom link
Abstract:
Chimeric antigen receptor (CAR)-engineered T cell therapies have transformed the standard of care for patients with B cell malignancies, but >50% of patients progress following therapy. In my talk, I will cover our recent work on the identification of CAR T regulatory (Treg) cells as limiting CAR T cell efficacy in large B cell lymphoma (LBCL). I will also present unpublished work on understanding additional T cell intrinsic factors impacting efficacy: CAR T cell expansion, persistence, and homing to the tumor. Using an endogenous T cell receptor (TCR) sequence as a ‘barcode’, we followed 17,479 unique CAR T cell clonotypes at the single-cell level from pre-manufacture apheresis and infusion products to tumor-involved lymph nodes and blood at peak and late expansion in 22 patients with LBCL or acute lymphoblastic leukemia (ALL) treated with CD19-CAR or CD19/CD22-CAR therapy. We found that T cells present in apheresis that preferentially expand during manufacturing primarily comprise T central memory cells. This work also linked pre-existing T regulatory (Treg) cells to poor response. In infusion products, CAR T conventional (non-Treg) cells with superior abilities to home to the tumor, expand, and persist post-infusion share features of activated T effector memory phenotype enriched for expression of BATF3 and high TCF4 transcription factor activity. Overall, lineage tracing at scale identified apheresis and infusion product cells with properties impacting efficacy, and also identified pre-existing Tregs as limiting efficacy of CAR T cell immunotherapies.
Biography:
Zinaida Good, Ph.D., is an Assistant Professor of Medicine in the Division of Immunology and Rheumatology and the Center for Biomedical Informatics Research at the Stanford University School of Medicine and the Director of the Cancer Cell Therapy Data Hub at the Stanford Center for Cancer Cell Therapy. Her research program focuses on understanding and enhancing engineered T cell immunotherapies for cancer and immune-mediated diseases through innovative computational approaches and systems immunology. During her postdoctoral training with Drs. Crystal Mackall and Sylvia Plevritis, Dr. Good performed fate mapping studies to identify features of optimal CAR T cells in large B cell lymphoma (LBCL) and diffuse midline glioma (DMG), and discovered the role of CAR T regulatory cells in resistance to CD19-CAR in LBCL. She earned her Ph.D. in Computational & Systems Immunology from Stanford University, where she trained with Drs. Garry Nolan and Sean Bendall and developed methods to build and leverage lymphocyte differentiation trajectories in health and cancer. Dr. Good's background in experimental immunology and oncology combines two years of experience in Discovery Oncology at Genentech with B.S. and M.S. degrees in Microbiology & Immunology from the University of British Columbia, where she investigated mechanisms of T cell memory with Dr. Michael Gold. Dr. Good’s work includes 4 first-author papers (Nature Medicine 2018 & 2022, Nature Biotechnology 2019, Trends in Immunology 2019), 17 co-authored papers (including Nature 2019, 2022, 2024, Science 2021, Nature Methods 2016, 2022, and NEJM 2024), and 2 patent applications. Her research is supported by the NIH Pathway to Independence Award, Parker Institute for Cancer Immunotherapy Bridge Fellowship, American Cancer Society Institutional Research Grant, and Parker Institute for Cancer Immunotherapy Innovation Challenge Grant. Dr. Good has been named an Arthur & Sandra Irving Cancer Immunology Fellow in 2022 and an AACR Woman in Cancer Research Scholar in 2024.