Single Cell Analysis of Response and Toxicity Following CD19 CAR T-Cell Therapy in Lymphoma
3PM CDT / 4PM EDT / 1PM PDT, May 24, 2023
The autologous chimeric antigen receptor (CAR) T cell therapies aimed at targeting CD19 have demonstrated a remarkable degree of efficacy in the management of relapsed/refractory large B cell lymphomas (LBCLs). However, despite impressive improvements in patient outcomes, the majority of patients do not have durable responses and treatment-associated adverse events, such as immune effector cell-associated neurotoxicity syndrome (ICANS), represent a significant clinical challenge. Failure of CAR T-cell therapy can be multifaceted and related to the quality of the T-cells at the time of apheresis, the associated functional heterogeneity of the CAR T-cell infusion product, and tumor and tumor microenvironment characteristics that may limit in vivo expansion and T-cell effector function. Toxicities are driven by a confluence of factors related to the activity of the CAR T-cell product and host immune cells. A central approach to uncovering mechanisms of resistance and toxicity has been the use of single cell RNA-sequencing (scRNA-seq) to analyze the various compartments (apheresis product, infusion product, post-infusion CAR T-cells, tumor).
Creative BioMart invited Dr. Michael R. Green to join us to provide an overview of scRNA-seq studies that have improved our understanding of CAR T-cell therapy and informed novel approaches to therapeutically target their mechanistic underpinnings.
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Michael R. Green, Ph.D.
Associate Professor & Director
Translational and Laboratory Research, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Dr. Green obtained his Bachelor of Biomedical Sciences at Victoria University of Wellington in New Zealand, a Ph.D. in Molecular Genetics from Griffith University in Australia, and completed post-doctoral training at the Dana-Farber Cancer Institute and Stanford University School of Medicine.
The mission of the Green Laboratory is to improve the survival and quality of life for people suffering from B-cell malignancies by developing innovative therapeutic interventions that are driven by a deep mechanistic understanding of normal and malignant immune cell biology. This is achieved by integrating knowledge from cutting-edge ‘omics’ approaches, primary patient biopsies, patient-derived xenograft models, transgenic mouse models, cell lines, and CRISPR/Cas9 gene editing experiments to characterize the function of important genetic, epigenetic, and immunological alterations in B-cell lymphoma and its tumor microenvironment. The ultimate goal is to harness this information to identify and develop new rationally targeted therapeutic strategies.