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源自人类多能干细胞的现成嵌合抗原受体免疫细胞。

Off-the-Shelf Chimeric Antigen Receptor Immune Cells from Human Pluripotent Stem Cells.

作者信息

Cao Handi, Sugimura Ryohichi

机构信息

School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

出版信息

Cancer Treat Res. 2022;183:255-274. doi: 10.1007/978-3-030-96376-7_9.

Abstract

Autologous chimeric antigen receptor (CAR) T cells have expanded the scope and therapeutic potential of anti-cancer therapy. Nevertheless, autologous CAR-T therapy has been challenging due to labor some manufacturing processes for every patient, and the cost due to the complexity of the process. Moreover, T cell dysfunction results from the immunosuppressive tumor microenvironment in certain patients. Considering technical challenges in autologous donors, the development of safe and efficient allogeneic CAR-T therapy will address these issues. Since the advent of the generation of immune cells from pluripotent stem cells (PSCs), numerous studies focus on the off-the-shelf generation of CAR-immune cells derived from the universal donor PSCs, which simplifies the manufacturing process and standardizes CAR-T products. In this review, we will discuss advances in the generation of immune cells from PSCs, together with the potential and perspectives of CAR-T, CAR-macrophages, and CAR-natural killer (NK) cells in cancer treatment. The combination of PSC-derived immune cells and CAR engineering will pave the way for developing next-generation cancer immunotherapy.

摘要

自体嵌合抗原受体(CAR)T细胞扩大了抗癌治疗的范围和治疗潜力。然而,自体CAR-T疗法一直面临挑战,因为为每个患者进行的制造过程繁琐,且由于过程复杂导致成本高昂。此外,在某些患者中,T细胞功能障碍是由免疫抑制性肿瘤微环境引起的。考虑到自体供体存在的技术挑战,安全有效的同种异体CAR-T疗法的开发将解决这些问题。自从从多能干细胞(PSC)生成免疫细胞以来,众多研究聚焦于从通用供体PSC现成生成CAR免疫细胞,这简化了制造过程并使CAR-T产品标准化。在本综述中,我们将讨论从PSC生成免疫细胞的进展,以及CAR-T、CAR巨噬细胞和CAR自然杀伤(NK)细胞在癌症治疗中的潜力和前景。PSC衍生的免疫细胞与CAR工程的结合将为开发下一代癌症免疫疗法铺平道路。

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