Mechanism Efficacy and Key Challenges of CAR-T Cell Therapy in Hematological Malignancies

Abstract

Chimeric Antigen Receptor T (CAR-T) cell therapy has achieved a revolutionary breakthrough in the immunotherapy of hematologic malignancies, significantly improving outcomes for patients with refractory or relapsed diseases. This paper systematically elaborates on the mechanism, efficacy and key challenges of CAR-T cell therapy. This paper first detail modular structure of CAR (antigen-binding, spacer, transmembrane, and signaling domains) and its five-generation iterative development, highlighting second-generation CARs as the most clinically applied due to added costimulatory domains. It then clarifies CAR-T’s three-step killing mechanism and summarizes efficacy in major hematological malignancies: CD19-CAR-T achieves over 90% complete remission with R/R B-cell ALL; progress is made in acute myeloid leukemia via targets like CD33 and CD123; and BCMA-CAR-T shows 86% response rate in multiple myeloma. Cytokine release syndrome, neurotoxicity, antigen escape, manufacturing logistics, and high costs are the key challenges. This paper provides a comprehensive summary of CAR-T therapy, offering valuable insights for clinical application optimization and overcoming current limitations.