从诱导多能干细胞中生成通用嵌合抗原受体表达细胞产品:超越自体CAR-T细胞。
Generating universal chimeric antigen receptor expressing cell products from induced pluripotent stem cells: beyond the autologous CAR-T cells.
发表日期:2023 Feb 21
作者:
Xinyue Deng, Jianfeng Zhou, Yang Cao
来源:
CHINESE MEDICAL JOURNAL
摘要:
采用养护型治疗免疫细胞如嵌合型抗原受体(CAR)T细胞和自然杀伤细胞,已经为顽固性淋巴瘤治疗建立了一代基于精准医疗的新突破。目前,充分研究的方法集中于自体细胞,因为它们的免疫原性低,但它们受到高成本、加工时间和某些患者原始细胞不足的严格限制。诱导性多能干细胞(iPSCs)是理论上能产生无限分化的免疫细胞的细胞来源。基于上述事实,结合iPSC技术和CAR设计,可以生产一系列高度可控和经济的“现场”药物。通过在遗传水平上进行失活或过度表达,制造低免疫原性的iPSCs,然后以CAR武装派生的细胞,已经成为一种“即用型”策略,可以在更广泛的患者范围内高效安全地消灭肿瘤细胞。本综述描述了这种方法的合理性、可行性、优越性和缺点,总结了当前的实践和相关研究进展,并提供了个性化细胞治疗可能的新途径。
版权所有©2023年中国医学会,由沃尔特斯·克鲁尔公司出版,在CC-BY-NC-ND许可下生产。
Adoptive therapeutic immune cells, such as chimeric antigen receptor (CAR)-T cells and natural killer cells, have established a new generation of precision medicine based on which dramatic breakthroughs have been achieved in intractable lymphoma treatments. Currently, well-explored approaches focus on autologous cells due to their low immunogenicity, but they are highly restricted by the high costs, time consumption of processing, and the insufficiency of primary cells in some patients. Induced pluripotent stem cells (iPSCs) are cell sources that can theoretically produce indefinite well-differentiated immune cells. Based on the above facts, it may be reasonable to combine the iPSC technology and the CAR design to produce a series of highly controllable and economical "live" drugs. Manufacturing hypoimmunogenic iPSCs by inactivation or over-expression at the genetic level and then arming the derived cells with CAR have emerged as a form of "off-the-shelf" strategy to eliminate tumor cells efficiently and safely in a broader range of patients. This review describes the reasonability, feasibility, superiority, and drawbacks of such approaches, summarizes the current practices and relevant research progress, and provides insights into the possible new paths for personalized cell-based therapies.Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.