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基因工程化 CAR-T 与 TCR-T 细胞制备与应用的当前与未来理念

英文原题:Current and future concepts for the generation and application of genetically engineered CAR-T and TCR-T cells.

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Current and future concepts for the generation and application of genetically engineered CAR-T and TCR-T cells.

PubMed 2023/03/06(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

过去几年,过继性细胞疗法(ACT)在免疫肿瘤学研发管线中的新治疗策略数量急剧增加。

中文摘要

近年来,过继细胞治疗(ACT)免疫肿瘤学领域的新型治疗方法显著增加,主要得益于嵌合抗原受体(CAR)T细胞疗法近期获批,以及其治疗某些血液系统肿瘤的显著疗效。ACT领域重点关注T细胞,以及如何通过基因修饰使其靶向并杀伤肿瘤细胞。目前使用的基因工程化T细胞装配了人工CAR或T细胞受体(TCR)。两种策略各有优势和局限。虽然CAR-T疗法已用于临床,但治疗实体瘤仍面临挑战。新一代CAR-T细胞设计可能克服这些障碍。此外,CAR受限于只能识别表面抗原;靶向胞内抗原的基因工程TCR-T细胞可能具备治疗实体瘤所需的特性。本综述总结CAR-T和TCR-T技术的主要进展,并介绍正在开展的临床试验、讨论当前挑战及评估该领域未来方向。

展开英文摘要原文

Adoptive cell therapy (ACT) has seen a steep rise of new therapeutic approaches in its immune-oncology pipeline over the last years. This is in great part due to the recent approvals of chimeric antigen receptor (CAR)-T cell therapies and their remarkable efficacy in certain soluble tumors. A big focus of ACT lies on T cells and how to genetically modify them to target and kill tumor cells. Genetically modified T cells that are currently utilized are either equipped with an engineered CAR or a T cell receptor (TCR) for this purpose. Both strategies have their advantages and limitations. While CAR-T cell therapies are already used in the clinic, these therapies face challenges when it comes to the treatment of solid tumors. New designs of next-generation CAR-T cells might be able to overcome these hurdles. Moreover, CARs are restricted to surface antigens. Genetically engineered TCR-T cells targeting intracellular antigens might provide necessary qualities for the treatment of solid tumors. In this review, we will summarize the major advancements of the CAR-T and TCR-T cell technology. Moreover, we will cover ongoing clinical trials, discuss current challenges, and provide an assessment of future directions within the field.

论文信息

作者
Hiltensperger M、Krackhardt AM
单位
German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany.Germany
文献类型
综述 · 非美国政府资助研究
期刊
Frontiers in immunology2023
原文标识
PubMed 36949949 · DOI 10.3389/fimmu.2023.1121030