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Induced Pluripotent Stem Cells (iPSCs) Provide a Potentially Unlimited T Cell Source for CAR-T Cell Development and Off-the-Shelf Products
Pharmaceutical Research ( IF 3.5 ) Pub Date : 2021-06-10 , DOI: 10.1007/s11095-021-03067-z
Muhammad Sadeqi Nezhad 1 , Meghdad Abdollahpour-Alitappeh 2 , Behzad Rezaei 3 , Mahboubeh Yazdanifar 4 , Alexander Marcus Seifalian 5
Affiliation  

Chimeric antigen receptor T (CAR-T) cell therapy has been increasingly conducted for cancer patients in clinical settings. Progress in this therapeutic approach is hampered by the lack of a solid manufacturing process, T lymphocytes, and tumor-specific antigens. T cell source used in CAR-T cell therapy is derived predominantly from the patient’s own T lymphocytes, which makes this approach impracticable to patients with progressive diseases and T leukemia. The generation of autologous CAR-T cells is time-consuming due to the lack of readily available T lymphocytes and is not applicable for third-party patients. Pluripotent stem cells, such as human induced pluripotent stem cells (hiPSCs), can provide an unlimited T cell source for CAR-T cell development with the potential of generating off-the-shelf T cell products. T-iPSCs (iPSC-derived T cells) are phenotypically defined, expandable, and as functional as physiological T cells. The combination of iPSC and CAR technologies provides an exciting opportunity to oncology and greatly facilitates cell-based therapy for cancer patients. However, T-iPSCs, in combination with CARs, are at the early stage of development and need further pre-clinical and clinical studies. This review will critically discuss the progress made in iPSC-derived T cells and provides a roadmap for the development of CAR iPSC-derived T cells and off-the-shelf T-iPSCs.



中文翻译:

诱导多能干细胞 (iPSC) 为 CAR-T 细胞开发和现成产品提供潜在无限的 T 细胞来源

嵌合抗原受体 T (CAR-T) 细胞疗法越来越多地用于临床环境中的癌症患者。由于缺乏可靠的制造工艺、T 淋巴细胞和肿瘤特异性抗原,这种治疗方法的进展受到阻碍。CAR-T 细胞疗法中使用的 T 细胞来源主要来自患者自身的 T 淋巴细胞,这使得这种方法对患有进行性疾病和 T 白血病的患者不切实际。由于缺乏现成的 T 淋巴细胞,自体 CAR-T 细胞的生成非常耗时,并且不适用于第三方患者。多能干细胞,如人类诱导多能干细胞(hiPSCs),可以为 CAR-T 细胞开发提供无限的 T 细胞来源,具有产生现成 T 细胞产品的潜力。T-iPSC(iPSC 衍生的 T 细胞)具有表型定义、可扩展性和与生理性 T 细胞一样的功能。iPSC 和 CAR 技术的结合为肿瘤学提供了一个令人兴奋的机会,并极大地促进了癌症患者的细胞治疗。然而,T-iPSCs 与 CARs 的结合尚处于发展的早期阶段,需要进一步的临床前和临床研究。本综述将批判性地讨论 iPSC 衍生 T 细胞的进展,并为 CAR iPSC 衍生 T 细胞和现成 T-iPSC 的发展提供路线图。处于开发的早期阶段,需要进一步的临床前和临床研究。本综述将批判性地讨论 iPSC 衍生 T 细胞的进展,并为 CAR iPSC 衍生 T 细胞和现成 T-iPSC 的发展提供路线图。处于开发的早期阶段,需要进一步的临床前和临床研究。本综述将批判性地讨论 iPSC 衍生 T 细胞的进展,并为 CAR iPSC 衍生 T 细胞和现成 T-iPSC 的发展提供路线图。

更新日期:2021-06-11
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