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中华细胞与干细胞杂志(电子版) ›› 2022, Vol. 12 ›› Issue (04) : 250 -256. doi: 10.3877/cma.j.issn.2095-1221.2022.04.009

综述

TCR-T治疗中靶点选择的策略
吴素馨1, 叶韵斌1,()   
  1. 1. 350014 福州,福建医科大学基础医学院;350014 福州,福建医科大学肿瘤临床医学院 福建省肿瘤医院肿瘤免疫学研究室;350014 福州,福建省肿瘤转化医学重点实验室
  • 收稿日期:2022-04-29 出版日期:2022-08-01
  • 通信作者: 叶韵斌
  • 基金资助:
    福建省科技创新联合资金资助项目(2018Y9108)

Strategies for target selection in TCR-T therapy

Suxin Wu1, Yunbin Ye1,()   

  1. 1. the School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350014, China; Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Tumor Immunology Laboratory, Fuzhou 350014, China; Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China
  • Received:2022-04-29 Published:2022-08-01
  • Corresponding author: Yunbin Ye
引用本文:

吴素馨, 叶韵斌. TCR-T治疗中靶点选择的策略[J]. 中华细胞与干细胞杂志(电子版), 2022, 12(04): 250-256.

Suxin Wu, Yunbin Ye. Strategies for target selection in TCR-T therapy[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2022, 12(04): 250-256.

T细胞受体工程化T细胞(TCR-T)治疗是目前肿瘤免疫细胞过继治疗研究领域的热点之一,近年,TCR-T治疗取得了突破性进展,在肿瘤免疫治疗中发挥越来越重要的作用。本文将综述目前TCR-T基础研究和临床应用方面的进展,分析不同类型肿瘤抗原对TCR-T治疗有效性的影响,为癌症细胞免疫治疗提供新思路。

T cell receptor-engineered T cell (TCR-T) therapy is one of the hot spots in the field of adoptive cell immunotherapies for cancer. In recent years, TCR-T therapy has made breakthrough progress and is playing an increasingly important role in the cancer therapy. Here, we analyze the role of different kinds of tumor antigens on the effectivity of TCR-T therapy by reviewing the current progress of TCR-T in basic researches and clinical trials, so as to provide new ideas for cellular immunotherapy to cancer.

图1 TCR-T细胞的制备流程注:DC细胞为树突状细胞,TCR为T细胞受体,Tetramer为四聚体,dextramer为多聚体
表1 TCR-T不同靶点的特点
表2 TCR-T临床试验登记表
项目注册号 TCR-T靶点 肿瘤类型 研究机构 阶段
NCT03691376 NY-ESO-1肿瘤相关抗原 顺铂耐药的癌症 美国罗斯维尔癌症中心 Phase1
NCT03029273 NY-ESO-1肿瘤相关抗原 复发性非小细胞肺癌 中国广州医科大学第一附属医院 Phase1
广州市呼吸疾病研究所
NCT02588612 NY-ESO-1肿瘤相关抗原 非小细胞肺癌 美国葛兰素史克公司 Phase1
NCT03168438 NY-ESO-1肿瘤相关抗原 NY-ESO-1和/或LAGE-1a阳性复发和难治性多发性骨髓瘤 美国葛兰素史克公司 Phase1
NCT04318964 NY-ESO-1肿瘤相关抗原 软组织肉瘤 中国中山大学 Phase1
NCT03462316 NY-ESO-1肿瘤相关抗原 骨肉瘤/软组织肉瘤 中国中山大学 Phase1
NCT02992743 NY-ESO-1肿瘤相关抗原 NY-ESO1阳性脂肪肉瘤 美国葛兰素史克公司 Phase2
NCT03941626 NY-ESO-1肿瘤相关抗原 食管癌、肝癌、神经胶质瘤、胃癌 中国河南省人民医院 Phase2
NCT05066165 WT1肿瘤相关抗原 急性髓系白血病 美国佛罗里达州坦帕市研究基地 Phase2
NCT02550535 WT1肿瘤相关抗原 骨髓增生异常综合征、急性髓系白血病 英国布里斯托尔大学医院等 Phase2
NCT05035407 KK-LC-1肿瘤相关抗原 肺癌 美国马里兰州贝塞斯达国家卫生研究院临床中心 Phase1
NCT03778814 KK-LC-1肿瘤相关抗原 非小细胞肺癌 中国广州医科大学第二附属医院 Phase1
NCT04639245 MAGE-A1肿瘤相关抗原 乳腺癌、肺癌、膀胱移行细胞癌 美国华盛顿大学癌症协会 Phase2
NCT04729543 MAGE-C2肿瘤相关抗原 黑色素瘤、葡萄膜黑色素瘤、头颈部癌症 荷兰鹿特丹伊拉斯谟医疗中心 Phase2
NCT04809766 间皮素肿瘤相关抗原 转移性胰管腺癌、IV期胰腺癌 美国华盛顿大学癌症协会 Phase1
NCT03638206 肿瘤相关抗原 淋巴瘤、骨髓白血病、胃癌等16种肿瘤 中国郑州大学第一附属医院 Phase2
NCT04156217 EBV病毒抗原 EBV相关肿瘤 中国河北燕达陆道培医院 Phase1
NCT03925896 EBV病毒抗原 鼻咽癌 中国中山大学癌症研究中心 Phase1
NCT03648697 EBV病毒抗原 鼻咽癌 中国福建省肿瘤医院 Phase2
NCT04139057 EBV病毒抗原 头部和颈部鳞状细胞癌 中国广州市第八人民医院 Phase2
NCT04509726 EBV病毒抗原 鼻咽癌 中国重庆新桥医院肿瘤科 Phase2
NCT04411134 HPV病毒抗原 宫颈上皮内瘤变 美国马里兰州贝塞斯达 Phase1
国家卫生研究院临床中心
NCT02719782 HBV病毒抗原 复发性肝细胞癌 中国中山大学第三附属医院 Phase1
NCT04677088 HBV病毒抗原 复发性肝细胞癌 中国中山大学第一附属医院 Phase1
NCT04476251 HPV病毒抗原 子宫颈肿瘤 美国马里兰州贝塞斯达 Phase1
国家卫生研究院临床中心
NCT04015336 HPV病毒抗原 人类乳头状病毒感染的各种疾病 美国马里兰州贝塞斯达 Phase1
国家卫生研究院临床中心
NCT03578406 HPV病毒抗原 子宫颈癌、头部和颈部鳞状细胞癌 中国重庆新桥医院 Phase1
NCT03578406 HPV病毒抗原 子宫颈癌、头部和颈部鳞状细胞癌 中国重庆新桥医院 Phase1
NCT05122221 HPV病毒抗原 子宫颈癌、神经癌、头部和颈部癌症 中国郑州大学第一附属医院 Phase1
NCT03197025 HPV病毒抗原 人乳头瘤病毒阳性鳞状上皮内病变 美国马里兰州贝塞斯达 Phase1
国家卫生研究院临床中心
NCT02858310 HPV病毒抗原 HPV相关肿瘤 美国马里兰州贝塞斯达 Phase2
国家卫生研究院临床中心
NCT03937791 HPV病毒抗原 鳞状上皮内病变 美国马里兰州国家卫生研究院临床中心 Phase2
NCT02280811 HPV病毒抗原 阴道癌、宫颈癌、肛门癌、阴茎癌、口咽癌 美国马里兰州国立卫生研究院 Phase2
NCT04044950 HPV病毒抗原 乳头瘤病毒感染、乳头瘤病毒感染 美国马里兰州贝塞斯达 Phase2
国家卫生研究院临床中心
NCT04153279 CMV病毒抗原 CMV相关肿瘤 中国河北燕达陆道培医院 Phase1
NCT05140187 CMV病毒抗原 造血干细胞移植后巨细胞病毒感染 中国人民解放军总医院 Phase1
NCT05089838 CMV病毒抗原 CMV相关肿瘤 中国北京大学血液学研究所、北京大学人民医院 Phase1
NCT04745403 HBV病毒抗原 肝细胞癌 新加坡综合医院 Phase1
NCT02686372 HBV病毒抗原 肝细胞癌 中山大学附属第一医院 Phase1
NCT03980691 HIV病毒抗原 HIV/AIDS 中国广州市第八人民医院 Phase1
NCT00991224 HIV病毒抗原 HIV感染者 美国宾夕法尼亚大学 Phase1
NCT03747484 MCPyV病毒抗原 转移性默克尔细胞癌 美国华盛顿大学癌症协会 Phase2
NCT03891706 肿瘤新抗原 实体瘤 中国中山大学肿瘤治疗中心 Phase1
NCT03970382 肿瘤新抗原 实体瘤 美国加州大学 Phase1
NCT04520711 肿瘤新抗原 恶性上皮肿瘤 美国普罗维登斯波特兰医疗中心 Phase1
NCT04680416 肿瘤新抗原 肾透明细胞癌 美国华盛顿大学医学院 /
NCT05124743 肿瘤新抗原 卵巢癌、子宫内膜癌、结肠直肠癌、胆管癌、非小细胞肺癌、胰腺癌 美国安德森癌症中心 /
NCT04464889 HA-1H 同种异体造血干细胞移植后复发或持续性血液系统恶性肿瘤 荷兰莱顿大学医学中心 Phase1
NCT03326921 HA-1 多种白血病 美国华盛顿大学癌症协会 Phase1
NCT03392545 未知 恶性胶质瘤 中国北京天坛医院 Phase1
NCT03431311 TGFβII 结直肠癌 挪威奥斯陆大学医院 Phase2
图2 不同类型肿瘤抗原作为TCR-T靶点比例
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