Cao Handi, Sugimura Ryohichi
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Cancer Treat Res. 2022;183:255-274. doi: 10.1007/978-3-030-96376-7_9.
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.
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。