T细胞受体工程化T细胞疗法的临床研究及动物肿瘤模型的应用

王琨; 汪金姣; 王皞鹏

T细胞受体工程化T细胞疗法的临床研究及动物肿瘤模型的应用

上海科技大学生命科学与技术学院, 上海 201210

基金项目:

国家重点研发计划（No.2019YFA0111001）

详细信息

作者简介:
王琨: 王皞鹏:上海科技大学生命科学与技术学院教授、博士生导师。2003年毕业于南京大学匡亚明学院,获理学学士学位;2004年进入圣裘德儿童研究医院/田纳西健康医学中心攻读博士研究生学位;2009-2015年,加州大学旧金山分校博士后。2015年被上海科技大学聘为研究员、博士生导师。2015年入选"国家青年千人计划",2018年获得"中科院分子细胞科学卓越创新中心青年骨干"称号。

汪金姣: 王皞鹏教授长期聚焦于"T细胞信号转导与工程化"的研究,2018年利用CRISPR全基因组遗传筛选,系统性地研究了T细胞激活的分子机制,绘制了人类T细胞功能的调控图谱。该工作是世界上首次报道的基于T细胞功能调控的全基因组CRISPR筛选;2020年通过研究CAR受体蛋白在CAR-T中运输降解的调控机制,设计了一种新型的可循环CAR,显著地提高了CAR-T的体内持续能力和抗肿瘤效果,为防止CAR-T治疗后肿瘤的复发提供了新策略。可循环CAR-T技术已于2020年底成功完成技术转让,预计于2021年开展可循环CAR-T相关的临床试验。

王皞鹏: 作为课题组负责人正在主持1项科技部国家重点研发计划项目,1项国家自然科学基金面上项目,1项罗氏制药合作项目。目前已在Science,Cell,Immunity,Nature Method,PNAS,EMBO等国际期刊上发表论文25篇,其中第一作者文章5篇,共同通讯作者文章5篇,申请专利4项。

通讯作者:
王皞鹏, 教授

中图分类号: Q789;R730.51
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出版历程
- 收稿日期: 2021-05-30

Clinical Research on T Cell Receptor-Engineered T Cells Therapy and Application of Its Preclinical Animal Models

School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China

More Information

Corresponding author:
WANG Haopeng, 教授

摘要

摘要: T细胞受体工程化T细胞（T cell receptor-engineered T cells，TCR-T）疗法和嵌合抗原受体T细胞（chimeric antigen receptor T cells，CAR-T）疗法是2种过继性细胞疗法（adoptive cell therapy，ACT），它们通过基因修饰技术赋予天然T细胞特异性识别肿瘤的受体来治疗癌症。CAR-T疗法针对复发或难治性血液系统恶性肿瘤，尤其是在急性淋巴细胞白血病（acute lymphoblastic leukemia，ALL）的治疗中展现出令人瞩目的临床效果，但对实体瘤的治疗效果却不尽如人意。靶向肿瘤抗原的TCR-T疗法已在临床上证明可以有效治疗实体瘤，并取得了令人鼓舞的临床数据。但是，TCR-T疗法也面临一些挑战，例如靶向肿瘤抗原的选择、肿瘤特异性TCR的选择和优化、TCR-T的体内持久性和临床安全性等。综述TCR-T疗法的临床发展现状和其非临床研究动物模型的应用，并讨论了动物模型在克服当前限制性因素中的应用，以期待TCR-T疗法使更多肿瘤患者受益。
- TCR-T疗法 /
- 非临床研究动物模型 /
- 实体瘤
Abstract: T cell receptor-engineered T cells (TCR-T) and chimeric antigen receptor T cells (CAR-T) therapies are two main types of adoptive cell therapy(ACT), which can treat cancer by giving natural T cells specific recognition of tumor receptors through gene modification technique. CAR-T therapy has achieved remarkable success in relapsed or refractory hematological malignancies, especially in the treatment of acute lymphoblastic leukemia (ALL), yet with less effect on solid tumors. TCR-T therapy has displayed some advantage over CAR-T therapy in treating solid tumors with inspiring clinical data. However, TCR-T therapy is faced with some challenges, including the selection of tumor-specific/associated antigens, selection and optimization of tumor-specific TCR, the persistence of TCR-T, and the safety of TCR-T therapy. This paper reviews the current development of TCR-T therapy and application of its preclinical animal models,and also discusses the progress made in the research on preclinical animal models employed to overcome the restrictive factors of TCR-T therapy, in the hope that TCR-T therapy will eventually benefit more cancer patients in the future.
- TCR-T cell therapy /
- preclinical animal model /
- solid tumor

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