肿瘤细胞治疗研究
英文原题：CAR T cells in lung cancer: Targeting tumor-associated antigens to revolutionize immunotherapy.
CAR T cells in lung cancer: Targeting tumor-associated antigens to revolutionize immunotherapy.
经工程改造以靶向并杀伤肿瘤细胞的肿瘤靶向 T 细胞通过嵌合抗原受体（CAR）T 细胞治疗彻底改变了肿瘤治疗，尤其是在血液系统恶性肿瘤中。
靶向肿瘤并经工程化改造以杀伤肿瘤细胞的 T 细胞，尤其通过嵌合抗原受体（CAR）T 细胞疗法，已改变血液系统恶性肿瘤的治疗。然而，由于肿瘤微环境（TME）、抗原异质性和 T 细胞浸润受限，这些成功经验难以推广至肺癌。本综述评估应对这些障碍的当前策略，重点关注肿瘤相关抗原（TAA）靶向优化，例如表皮生长因子受体（EGFR）、黏蛋白 1（MUC1）和间皮素（MSLN）；这些抗原在肺癌中常过表达，是 CAR-T 治疗有希望的靶点。文章讨论 CAR-T 工程化近期进展，包括增强共刺激分子、分泌细胞因子的 CAR-T 细胞，以及提高 T 细胞在免疫抑制环境中耐受性的工程化改造。此外，综述还评估免疫检查点抑制剂联合疗法及近期发表的肺癌 CAR-T 临床试验。通过分析抗原选择、免疫逃逸，以及增强 T 细胞持久性和肿瘤浸润的策略，本文为优化 CAR-T 肺癌治疗提供见解。
Tumor-targeted T cells engineered for targeting and killing tumor cells have revolutionized cancer treatment, specifically in hematologic malignancies, through chimeric antigen receptor (CAR) T cell therapy. However, the migration of this success to lung cancer is challenging due to the tumor microenvironment (TME), antigen heterogeneity, and limitations of T cell infiltration. This review aims to evaluate current strategies addressing these barriers, focusing on the optimization of tumor-associated antigen (TAA) targeting, such as epidermal growth factor receptor (EGFR), mucin-1 (MUC1), and mesothelin (MSLN), which are frequently overexpressed in lung cancer and offer promising targets for CAR T-cell therapy. In this review, we discuss recent progress in CAR T cell engineering, applying enhanced costimulatory molecules, cytokine-secreting CAR T cells, and engineered modifications to improve T cell resilience in immunosuppressive environments. Additionally, this review also evaluates combination therapies of immune checkpoint inhibitors and recently published clinical trials on lung cancer with CAR T cells. We offer insights into the way to optimize CAR T cell therapy for lung cancer by analyzing antigen selection, immune evasion, and the strategies to enhance T cell persistence and tumor infiltration.
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