推动 CAR-T 疗法治疗实体瘤：从障碍到临床进展

Therapy with chimeric antigen receptor (CAR)-T cells has revolutionized the treatment of hematological malignancies.

However, their application in solid tumors remains a formidable challenge due to obstacles such as the immunosuppressive tumor microenvironment, tumor heterogeneity, and limited T cell persistence. Although second- and third-generation CAR-T cells have shown restricted efficacy in clinical trials, next-generation strategies-including cytokine-armored CAR-T cells (e. g. , IL-15, IL-7/CCL19), logic-gated systems, and localized delivery approaches-demonstrate promising potential to overcome these limitations.

This review examines the major barriers impeding CAR-T cell efficacy in solid tumors, evaluates clinical outcomes from conventional CAR constructs, and highlights innovative strategies being tested in recent clinical trials. Key advances discussed include the use of dominant-negative receptors (e. g. , TGF RII) to combat immunosuppression and the co-expression of bispecific T cell engagers (BiTEs) to address antigen escape.