Antigen escape in CAR-T cell therapy: Mechanisms and overcoming strategies
Chimeric antigen receptor T (CAR-T) cell therapy has shown promise in treating hematological malignancies and certain solid tumors. However, its efficacy is often hindered by negative relapses resulting from antigen escape. This review firstly elucidates the mechanisms underlying antigen escape during CAR-T cell therapy, including the enrichment of pre-existing target-negative tumor clones, antigen gene mutations or alternative splicing, deficits in antigen processing, antigen redistribution, lineage switch, epitope masking, and trogocytosis-mediated antigen loss. Furthermore, we summarize various strategies to overcome antigen escape, evaluate their advantages and limitations, and propose future research directions. Thus, we aim to provide valuable insights to enhance the effectiveness of CAR-T cell therapy. • Antigen escape is one of the most significant limitations of CAR-T therapy. • Multiple mechanisms of antigen escape in CAR-T cell therapy have been identified. • Combination approaches are a feasible strategy for addressing antigen escape. • Future directions for developing more effective CAR-T cell therapies hinge on addressing antigen escape.