决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Current and future concepts for the generation and application of genetically engineered CAR-T and TCR-T cells.
Current and future concepts for the generation and application of genetically engineered CAR-T and TCR-T cells.
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。
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。
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.
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