Single Cell Analysis of Response and Toxicity Following CD19 CAR T-Cell Therapy in Lymphoma

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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