Adaptive T cell immunotherapy in cancer

Adaptive T cell immunotherapy in cancer
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癌症的适应性 T 细胞免疫疗法

DOI:
10.1007/s11427-020-1713-9
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发表时间:
2020-07
期刊:
Science China Life Sciences
影响因子:
--
通讯作者:
Weidong Han
Weidong Han
中科院分区:
其他
文献类型:
--
作者:
Dongdong Ti;Miaomiao Bai;Xiaolei Li;Jianshu Wei;Deyun Chen;Zhiqiang Wu;Yao Wang;Weidong Han

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受损的肿瘤特异性效应T细胞有助于肿瘤进展和不利的临床结果。过继性T细胞疗法(ACT)作为一种补偿性T细胞依赖性癌症免疫编辑策略,已经取得了令人鼓舞的治疗效果,目前已成为癌症治疗和研究的中心。ACT涉及具有固有肿瘤反应性的肿瘤浸润淋巴细胞(TIL)或经遗传修饰以表达同源嵌合抗原受体或T细胞受体(CAR/TCR)的T细胞的体外刺激和扩增,随后将这些细胞被动转移到淋巴细胞耗尽的宿主中。在ACT过程中,致敏的T细胞必须对转化细胞提供高效和持久的免疫防御。深入了解这些活性药物的基本机制可以帮助我们改进当前的策略,并设计更好的下一代基于T细胞的免疫疗法。从这个角度来看,我们提供了一个不同的ACT策略的当前发展的概述,重点是前沿的临床试验,提供了一个原则的证明。同时,对ACT的决定因素进行了深入探讨,这将导致未来更合理、更有效和更广泛的应用。
Impaired tumor-specific effector T cells contribute to tumor progression and unfavorable clinical outcomes. As a compensatory T cell-dependent cancer immunoediting strategy, adoptive T cell therapy (ACT) has achieved encouraging therapeutic results, and this strategy is now on the center stage of cancer treatment and research. ACT involves theex vivostimulation and expansion of tumor-infiltrating lymphocytes (TILs) with inherent tumor reactivity or T cells that have been genetically modified to express the cognate chimeric antigen receptor or T cell receptor (CAR/TCR), followed by the passive transfer of these cells into a lymphodepleted host. Primed T cells must provide highly efficient and long-lasting immune defense against transformed cells during ACT. Anin-depth understanding of the basic mechanisms of these living drugs can help us improve upon current strategies and design better next-generation T cell-based immunotherapies. From this perspective, we provide an overview of current developments in different ACT strategies, with a focus on frontier clinical trials that offer a proof of principle. Meanwhile, insights into the determinants of ACT are discussed, which will lead to more rational, potent and widespread applications in the future.
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