CAR-T Cell Therapy for Solid Tumors: A Review of Challenges and Emerging Solutions

​​Chimeric antigen receptor (CAR)-T cell therapy is a promising immunotherapy for hematological malignancies. However, its application to solid tumors is limited by challenges such as the immunosuppressive tumor microenvironment, poor T-cell trafficking and infiltration, and on-target off-tumor toxicity. This review article discusses innovative strategies to address these limitations and enhance CAR-T cell efficacy against solid tumors. One approach involves engineering CAR-T cells to express checkpoint blockade inhibitors or dominant negative receptors to counteract immunosuppressive signals. Alternatively, CAR-T cells can be modified to secrete immunostimulatory cytokines or resist immunosuppressive factors like TGF-β. To improve T-cell trafficking and infiltration, regional delivery methods such as intrapleural or intracerebroventricular injection can be employed. Additionally, equipping CAR-T cells with chemokine receptors that match tumor-derived chemokines can enhance their homing ability. Overall, these emerging strategies hold the potential to overcome the current obstacles and expand the therapeutic applications of CAR-T cell therapy for solid tumors.