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:Adapting CAR-T and CAR-Treg cancer therapies for autoimmunity: innovations and challenges.
Adapting CAR-T and CAR-Treg cancer therapies for autoimmunity: innovations and challenges.
近年来,CAR-T 细胞、CAR工程化调节性T细胞(CAR-Treg)和造血干细胞(HSC)疗法的应用不断增长,这得益于对用于治疗癌症和自身免疫疾病的强效、抗原特异性T淋巴细胞的需求日益增加。
近年来,CAR-T 细胞、CAR 工程化调节性 T 细胞(CAR-Treg)和造血干细胞(HSC)疗法应用不断增加,原因是癌症和自身免疫病治疗都日益需要强效、抗原特异性的 T 淋巴细胞。本综述首先考察现有细胞疗法、生物学原理和作用机制,以及这些方法如何在癌症治疗中取得显著成功。随后讨论将这些策略用于渐进型和复发型多发性硬化(MS)及 1 型糖尿病(T1D)等自身免疫病的可能性。文章阐述 CAR-T 和 CAR-Treg 疗法的巨大前景,并强调 HSC 的作用,同时详细介绍作用机制、生产流程和正在开展的临床试验。综述还分析关键挑战,例如靶向及脱靶效应、对自体细胞来源的依赖、生产成本高和制备周期长。文章强调,需要持续开展研究,以推动这些疗法在不同医疗体系中更广泛地临床应用。
The application of Chimeric Antigen Receptor T-cell (CAR-T), CAR-engineered regulatory T cell (CAR-Treg) and hematopoietic stem cell (HSC) therapies has grown in recent years, driven by an increasing demand for robust, antigen-specific T lymphocytes for the treatment of both cancer and autoimmune diseases. This review begins by examining existing cell-based therapies, its biological principles and mechanisms, that have helped achieve notable success in treating cancer. The review then discusses the applicability of these approaches to autoimmune diseases such as progressive and relapsing Multiple Sclerosis (MS) and Type 1 Diabetes Mellitus (T1D). We discuss the substantial promise of CAR-T and CAR-Treg therapies and highlight the role of HSCs, while detailing their mechanism of action, manufacturing processes and ongoing clinical trials. We also examine key challenges such as on and off-target effects, dependence on autologous cell sources, high production costs, and lengthy manufacturing timelines. Our review underscores the need for continued research to facilitate broader clinical implementation of these therapies across diverse healthcare settings.
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