CELL INTELLIGENCE · 肿瘤细胞治疗研究

Lung carcinoma has consistently ranked as the most prevalent malignancy and foremost contributor to cancer-related mortality in global epidemiology. Despite the paradigm-shifting advancements in molecularly targeted therapies and immune checkpoint inhibitors (ICIs) for advanced-stage non-small cell lung cancer (NSCLC), clinical outcomes remain constrained by tumor recurrence and treatment resistance. Chimeric antigen receptor (CAR) T cell therapy, a revolutionary cellular immunotherapy modality, has demonstrated unprecedented clinical efficacy in hematological malignancies. Nevertheless, its clinical implementation in solid malignancies, particularly non-small cell lung cancer (NSCLC), remains hindered by some cardinal biological barriers including spatial heterogeneity of tumor-associated antigens, on-target/off-tumor toxicity risks, immunosuppressive tumor microenvironment (TME), inefficient T-cell trafficking, and T-cell dysfunction hallmarked by exhaustion and poor persistence signatures. This review aims to discuss the development of CAR-T cells for lung cancer from preclinical studies to ongoing clinical trials. Specifically, we summarize tumor-associated antigens in lung cancer, ongoing clinical trials, barriers to CAR-T cell therapy in lung cancer, and discuss potential strategies to improve therapeutic efficacy. We, therefore outline the trajectory of CAR-T cells that may evolve from promising experimental approaches to a standard modality for lung cancer therapy.