Work

Beyond CD19: Engineering next-generation CAR-T cell therapies for leukemia

Year: 2026

Type: article

Abstract: Despite the advances made in treating leukemia, relapse of the disease and the development of resistance to the treatments that were utilized still plague the field today, indicating the need for next-generation immunotherapies. Chimeric antigen receptor T cell (CAR-T) therapy has markedly transformed leukemia treatment, emerging as a promising therapeutic approach. Beyond the conventional CAR-T cell engineering targeting the cluster of differentiation 19 (CD19) antigen for leukemia treatment, this review also investigates the biological mechanisms behind the efficacy and failure of these treatments. Beyond these analyses are the engineering innovations that have been created to overcome these mentioned issues. Areas of focus for this review include next-generation CAR-T cell engineering, including developments utilizing dual targeting, logic gates, armored CAR-T cells, switchable CAR-T cells, universal CAR-T cells, allogeneic CAR-T cells, and CAR-T cells engineered with clustered regularly interspaced short palindromic repeats (CRISPR) technologies. Additionally, the role of emerging artificial intelligence-driven strategies for improving the design of CAR-T cells is also discussed. This review also highlights the significant limitations of CAR-T therapy, such as high cost, cytokine release syndrome, neurotoxicity, antigen escape, and resistance, which can contribute to cancer relapse. Rather than providing an overview of CAR-T cell therapy in general, this review aims to discuss the engineering solutions to these barriers, as well as the considerations regarding manufacturing, accessibility, regulation, and clinical translation of next-generation CAR-T cell therapies for the precision treatment of leukemia patients.

Source: Current Molecular Pharmacology

DOI: 10.1016/j.cmp.2026.09.006