Emerging Applications of CAR-T Cell Therapy in Overcoming Resistance and Expanding Targets in Hematologic Malignancies: Insights from Recent Research

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment outcomes of patients with hematologic malignancies, including B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (DLBCL), and multiple myeloma (MM). However, issues such as antigen escape, T-cell exhaustion, and the limited efficacy of CAR-T cells in acute myeloid leukemia (AML) and T-cell leukemias still persist. This review aims to summarize human trials and achievements from 2015 with a focus on the innovations within the last two years. We discuss strategies to overcome resistance, including multi-target CARs, next-generation constructs, and combination strategies to treat resistant cancers. We also explore the ways to increase safety and access, including allogeneic CAR-T options. In this article, we propose CRISPR-enhanced CARs and synthetic biology-based allogeneic systems to enhance the efficacy and accessibility of CAR-T therapy with the aim of moving the field of oncology towards durable cures.