Dual-target CAR-T cell therapy: A new strategy to improve the therapeutic effect of hematological malignancies

Chimeric antigen receptor T (CAR-T) cell therapy represents a significant advancement in tumor immunotherapy, demonstrating notable efficacy in the treatment of hematological malignancies. Nevertheless, single-target CAR-T therapy encounters several challenges, including antigen escape, on-target off-tumor toxicity, and tumor heterogeneity. To address these limitations, dual-target CAR-T cell therapy has been developed. By recognizing two tumor antigens, dual-target CAR-T therapy broadens the antigen recognition spectrum of CAR-T cells and substantially mitigates the risk of antigen escape. Additionally, the incorporation of logic gate control design enhances its precision and minimizes on-target off-tumor toxicity. This review provides a comprehensive analysis of various dual-target CAR-T cell types, including sequential CAR-T cells, dual-signal CARs, tandem CARs, AND-gate CARs, and inhibitory CARs, with a focus on their applications and therapeutic efficacy in hematological malignancies. Furthermore, this review provides an in-depth examination of the unique advantages, current research progress, and challenges associated with dual-target CAR-T cell therapy.