摘要
伴随对肺癌病理生理和发病机制的深入认识,肺癌治疗已进入一个新时代。目前,包括单克隆抗体靶向药物在内的免疫治疗药物越来越多地被用于恶性肿瘤的临床治疗,但仍有许多局限性。嵌合抗原受体修饰T细胞(Chime-ric antigen receptor modified T,CAR-T)是一种新型的过继性免疫治疗策略,不仅成功地用于治疗血液肿瘤,而且为包括肺癌在内的实体瘤的免疫治疗开辟了新的理论依据。然而,使用CAR-T细胞靶向肺癌治疗由于缺乏合适的肿瘤特异性抗原、免疫抑制性肿瘤微环境、肿瘤抗原逃逸以及脱靶效应等而变得非常复杂。本综述旨在系统阐释CAR-T细胞的基本结构和生成特征,总结了CAR-T细胞治疗肺癌临床试验中常见的肿瘤相关抗原,指出当前面临的挑战和新策略,以期为肺癌CAR-T细胞治疗的临床前及临床试验提供新的思路和方法。
With the deeper understanding of the pathophysiology and pathogenesis lung cancer treatment has entered a new era.At present,an increasing number of immunotherapeutic agents including monoclonal antibody-targeted drugs have been used in the clinical treatment of malignancy,but it still has many limitations.Chimeric antigen receptor-modified T(chime-ric antigen receptor modified T,CAR-T)cells,a novel adoptive immunotherapy strategy,have not only been used successfully against hematological tumors,but also opens up a new theoretical basis for the immunotherapy of solid tumors including lung cancer.However,targeting lung cancer-specific antigens using engineered CAR-T cells is complicated because of the lack of proper tumor-specific antigens,an immunosuppressive tumor microenvironment,tumor antigen escape,along with off-target effect,etc.This review aims to systematically explain the basic structure and generation characteristics of CAR-T cells,summarize the common tumor-associated antigens in clinical trials of CAR-T cells for the treatment of lung cancer,and point out the current challenges and new strategies,which might provide new ideas and approaches for preclinical and clinical trials of lung cancer.
作者
王彦哲
何思思
马虎
Wang Yanzhe;He Sisi;Ma Hu(Department of Thoracic Oncology,the Second Affiliated Hospital of Zunyi Medical University,Zunyi Guizhou 563099,China)
出处
《遵义医科大学学报》
2022年第2期258-265,共8页
Journal of Zunyi Medical University
基金
国家自然科学基金资助项目(NO:81660512)
贵州省科技厅项目(NO:黔科合基础[2020]1Z062)
遵义医科大学2020年研究生科研基金项目(NO:ZYK025)。
关键词
肺癌
嵌合抗原受体
T细胞
免疫治疗
lung cancer
chimeric antigen receptor
T cells
immunotherapy
