How to enhance the killing ability of CAR-T cells to solid tumors?

Chimeric antigen receptor T-cell (CAR-T) therapy is an innovative method of tumor immunotherapy. It has achieved excellent results in treating hematological malignancies and has been applied in a number of clinical situations. However, its therapeutic effect in solid tumors is still limited by multiple factors, including immunosuppression of the neoplastic microenvironment, target heterogeneity, insufficient penetration ability of CAR-T cells and poor persistence, etc. This study aims to explore effective approaches for enhancing the cytotoxicity of CAR-T cells against strong tumors. Through literature review and comprehensive analysis, this paper focuses on evaluating various enhancement methods, including optimizing the design of CAR structures (such as using costimulatory domain improvement, dual/multi-target CAR construction), synergistic therapy with combined immunomodulatory factors (such as IL-12, IL-18, IL-15) or antibody molecules, and targeting the tumor microenvironment, etc. Studies have pointed out that constructing CAR-T cells with stronger penetration, persistent activation ability and anti-exhaustion characteristics is a key direction to break through the bottleneck for treating strong tumors.This project provides theoretical assistance and strategic guidance. It helps us understand more deeply about the potential and problems of CAR-T cell therapy for solid neoplasms.