(CAR-)T cell dynamics following chimeric antigen receptor T cells for large B cell lymphoma: a translational tale.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy represents a breakthrough in the treatment of B-cell malignancies. CAR-T cells infusion generally follows a chemotherapy regimen whose lymphodepleting properties create a favorable environment for the expansion of engineered T cells. While this process appears straightforward, emerging evidence reveals that complex mechanisms, collectively representing immune dynamics following CAR-T cell infusion, influence CAR-T cells behavior. In advance of infusion, a final-product enriched with less stressed CAR-T cells can improve their expansion and persistence, providing a biological rationale for early apheresis and administration. Following infusion, the emergence of dysfunctional CAR-T subpopulations, like regulatory or NK-like CAR-T cells, can impair efficacy. The recovery of non-CAR transduced T cells adds further complexity, as these cells could either impact outcomes or exacerbate complications, such as infections or prolonged cytopenia. In this review, we summarize the latest advances in understanding the immune dynamics following CAR-T cell infusion for large B-cell lymphomas, with a focus on both CAR-engineered and native T cell populations, and their impact on treatment efficacy and patient outcomes.