Chimeric antigen receptor T-cell therapy: challenges and opportunities in lung cancer

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the paradigm in hematological malignancies treatment, driving an ever-expanding number of basic research and clinical trials of genetically engineering T cells to treat solid tumors. CAR T-cell therapies based on the antibodies targeting Mesothelin, CEA, EGFR, EGFR, MUC1, DLL3, and emerging novel targets provide promising efficacy for lung cancer patients. However, clinical application of CAR T-cell therapy against lung cancer remains limited on account of physical and immune barriers, antigen escape and heterogeneity, on-target off-tumor toxicity, and many other reasons. Understanding the evolution of CAR structure and the generalizable requirements for manufacturing CAR T cells as well as the interplay between lung tumor immunology and CAR T cells will improve clinical translation of this therapeutic modality in lung cancer. In this review, we systematically summarize the latest advances in CAR T-cell therapy in lung cancer, focusing on the CAR structure, target antigens, challenges, and corresponding new strategies.