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:A guide to CAR T cell therapies: development, current status and future prospects.
自 2017 年首次获得临床批准以来,嵌合抗原受体(CAR)T 细胞疗法已成为重定向免疫应答以对抗癌症的最有力手段之一。
自2017年首次获得临床批准以来,嵌合抗原受体(CAR)T细胞疗法已成为将免疫应答重定向至癌症的最强效治疗方式之一。基于数十年来T细胞生物学和合成免疫工程的基础发现,CAR-T细胞疗法改变了B细胞恶性肿瘤的治疗,使B细胞白血病、淋巴瘤和多发性骨髓瘤患者获得持久缓解。新一代CAR设计正在将这一方法拓展至自身免疫病和实体瘤。基因编辑、异基因制造和体内递送方面的创新正在改善CAR-T细胞疗法的可扩展性、安全性和可及性,但克服抗原异质性和肿瘤微环境屏障,以及促进CAR-T细胞长期持久性,仍是挑战。本综述总结奠定CAR-T细胞疗法基础的关键发现,并全面概述当前CAR设计原则、临床开发,以及旨在提高疗效、拓宽适应证并实现不同疾病类型持久免疫控制的新兴策略。
Since the first clinical approval in 2017, chimeric antigen receptor (CAR) T cell therapy has emerged as one of the most powerful modalities for redirecting the immune response against cancer. Building on decades of foundational discoveries in T cell biology and synthetic immunoengineering, CAR T cell therapy has transformed the treatment of B cell malignancies, resulting in durable remissions in patients with B cell leukaemias, lymphomas and multiple myeloma. Next-generation CAR designs are now expanding the reach of this approach into autoimmune disease and solid tumours. Innovations in gene editing, allogeneic manufacturing and in vivo delivery are improving the scalability, safety and accessibility of CAR T cell therapies, although challenges persist in overcoming antigen heterogeneity and tumour microenvironmental barriers and in promoting the long-term persistence of CAR T cells. In this Review, we summarize the key discoveries that laid the foundations for CAR T cell therapies and provide a broad overview of the current principles of CAR design, their clinical development and emerging strategies aimed at enhancing efficacy, broadening indications and achieving durable immune control across disease types.
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