CAR T-cells in hematologic malignancies: Advances, challenges, and future directions

Chimeric antigen receptor (CAR) T-cell therapy has transformed the management of hematologic malignancies, achieving high remission rates in relapsed or refractory B-cell acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma. By redirecting autologous or allogeneic T lymphocytes against tumor-associated antigens such as CD19 and TNFRSF17, CAR T-cells overcome resistance to conventional therapies. Progressive optimization of CAR design-from early constructs to armored and logic-gated platforms-has enhanced persistence, specificity, and safety. Pivotal trials and real-world evidence confirm durable responses, although challenges remain, including cytokine release syndrome, neurotoxicity, manufacturing complexity, high cost, and limited global access. Emerging strategies, such as multi-antigen targeting, gene editing technologies, and in vivo CAR delivery, aim to improve efficacy and scalability. Integration of artificial intelligence and point-of-care manufacturing may further streamline production and patient selection. Continued innovation will determine the long-term impact of CAR T-cell therapy as a scalable pillar of precision hematologic oncology.