T细胞受体基因工程T细胞治疗的现状与未来  

Current and Future Development of T Cell Receptor-Engineered T Cell Therapy

作　　者：王丹阳 熊昕昕 刘海平 周鹏辉 WANG Danyang;XIONG Xinxin;LIU Haiping;ZHOU Penghui(State Key Laboratory of Oncology in South China,Sun Yat-sen University Cancer Center,Guangzhou 510060,China;Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510055,China;Guangzhou FineImmu Biotechnology Co.,Ltd.,Guangzhou 510535,China)

机构地区：[1]华南肿瘤学国家重点实验室中山大学肿瘤防治中心,广东广州510060 [2]广东省人民医院广东医学科学院,广东广州510055 [3]广州泛恩生物科技有限公司,广东广州510535

出　　处：《药学进展》2021年第8期608-615,共8页Progress in Pharmaceutical Sciences

基　　金：国家重点研究发展计划(No.201610516);国家自然科学基金(No.81802853,No.81773052,No.81572806);中国博士后科学基金资助项目(No.2018M633237);广东省科技计划项目(No.2016A020215086,No.2017A030308007);广东省创新创业研究团队项目(No.2016ZT06S638);广东省医学科研基金项目(No.2016111214046444)。

摘　　要：免疫治疗为肿瘤的治疗带来了新的契机和希望,其中免疫检查点抑制剂、治疗性抗体、肿瘤疫苗、免疫调节剂、过继细胞治疗等显著改善了肿瘤患者的预后,部分晚期肿瘤患者获得了长期生存。T细胞受体基因工程T细胞(T cell receptor-engineered T cell,TCR-T)治疗是将识别肿瘤抗原的T细胞受体(T cell receptor,TCR)导入到患者的外周T细胞中,制备能够特异性识别肿瘤抗原的T细胞,然后将这些基因工程T细胞回输患者的治疗方法。该疗法采用天然的TCR信号,具有更高的治疗潜力和更低的毒性或副作用,并且TCR能够识别更多的肿瘤抗原,因此具有广泛的应用前景。目前,多项TCR-T治疗的临床研究正在开展,现有结果表明TCR-T具有较好的治疗效果,但也存在副作用等问题亟需解决。综述TCR-T治疗的临床研究进展、目前面临的挑战以及未来发展的方向。Immunotherapy has brought us new opportunities and hopes in cancer treatment,including immune checkpoint inhibitors,therapeutic antibodies,cancer vaccines,immune modulators and adoptive cell therapies,which have significantly improved prognosis of tumor patients and long-term survival of some advanced malignant tumor patients.T cell receptor-engineered T cell(TCR-T)therapy is a type of therapy that transforms T cell receptor(TCR)-recognizing tumor antigens into the patient,s peripheral T cells to produce T cells which can specifically recognize tumor antigens,with such genetically engineered T cells being then injected back into the patient.Due to the natural TCR signaling,better therapeutic efficacy,lower toxic or side effects and more options of targeting antigens,TCR-T therapy is believed to have a wide range of application.At present,a number of clinical studies on TCR-T therapy are underway,and the existing results show that TCR-T has a good therapeutic effect,though some problems such as side effects still remain to be addressed.This review focuses on the clinical research progress,current challenges and future development of TCR-T therapy.

关 键 词：T细胞受体基因工程T细胞 肿瘤抗原 肿瘤免疫治疗 

分 类 号：Q789[生物学—分子生物学] R730.51[医药卫生—肿瘤]