Research Progress On CAR-T In Treating NSCLC

As a subtype, non-small cell lung cancer (NSCLC) represents about 85% of all cases. This rate is largely due to the disease often being diagnosed at an advanced stage, the tendency for metastasis, and the development of resistance to treatments. While advancements in targeted therapies and immunotherapies have improved outcomes, challenges such as toxicity and tumor heterogeneity still persist. Chimeric antigen receptor T-cell (CAR-T) therapy, which has a breakthrough in the Leukemia, shows emerging potential in NSCLC despite limitations in solid tumor applications. This review summarizes recent progress in the CAR-T therapy for NSCLC, focusing on target selection, combination strategies, challenges, and future directions. Key targets under investigation include EGFR, MSLN, MUC1, PSCA, CD133+, EphA2, and B7-H3, which demonstrate varied efficacy in preclinical and early clinical studies. For instance, EGFR-targeted CAR-T cells reduced metastatic lesions and improved survival in murine models, while MSLN-directed therapy achieved partial remission in patients. Combination regimens with chemotherapy and radiotherapy, could enhance the constructed cell infiltration and improve the therapeutic efficacy. Despite these advances, challenges such as cytokine release syndrome (CRS), antigen heterogeneity, immunosuppressive microenvironments, and high costs hinder clinical translation. Innovative solutions like dual-target CAR-T cells, gene-edited constructs and personalized approaches leveraging liquid biopsy are under exploration. While this therapy for NSCLC is still under research, ongoing preclinical optimization and clinical trials highlight its transformative potential. Future efforts must prioritize multi-target strategies, synergistic combination therapies, and cost-effective manufacturing to treat NSCLC patients.