Prospects for Development of Induced Pluripotent Stem Cell-Derived CAR-Targeted Immunotherapies

IF 2.9 4区 医学 Q3 IMMUNOLOGY Archivum Immunologiae et Therapiae Experimentalis Pub Date : 2021-12-12 DOI:10.1007/s00005-021-00640-7
Roberta Mazza, John Maher
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引用次数: 11

Abstract

Technologies required to generate induced pluripotent stem cells (iPSC) were first described 15 years ago, providing a strong impetus to the field of regenerative medicine. In parallel, immunotherapy has finally emerged as a clinically meaningful modality of cancer therapy. In particular, impressive efficacy has been achieved in patients with selected haematological malignancies using ex vivo expanded autologous T cells engineered to express chimeric antigen receptors (CARs). While solid tumours account for over 90% of human cancer, they currently are largely refractory to this therapeutic approach. Nonetheless, given the considerable innovation taking place worldwide in the CAR field, it is likely that effective solutions for common solid tumours will emerge in the near future. Such a development will create significant new challenges in the scalable delivery of these complex, costly and individualised therapies. CAR-engineered immune cell products that originate from iPSCs offer the potential to generate unlimited numbers of homogeneous, standardised cell products in which multiple defined gene modification events have been introduced to ensure safety, potency and reproducibility. Here, we review some of the emerging strategies in use to engineer CAR-expressing iPSC-derived drug products.

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诱导多能干细胞衍生car靶向免疫疗法的发展前景
产生诱导多能干细胞(iPSC)所需的技术在15年前首次被描述,为再生医学领域提供了强大的推动力。与此同时,免疫疗法终于成为一种临床有意义的癌症治疗方式。特别是,使用体外扩增的自体T细胞来表达嵌合抗原受体(CARs),在某些血液系统恶性肿瘤患者中取得了令人印象深刻的疗效。虽然实体肿瘤占人类癌症的90%以上,但目前这种治疗方法在很大程度上是难治性的。尽管如此,鉴于CAR领域在世界范围内发生的重大创新,很可能在不久的将来出现针对普通实体肿瘤的有效解决方案。这种发展将为这些复杂、昂贵和个性化的治疗方法的可扩展提供带来重大的新挑战。源自多能干细胞的car工程免疫细胞产品有可能产生无限数量的同质、标准化细胞产品,其中引入了多个已定义的基因修饰事件,以确保安全性、效力和可重复性。在这里,我们回顾了一些用于设计car表达ipsc衍生药物产品的新兴策略。
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来源期刊
CiteScore
5.90
自引率
0.00%
发文量
26
审稿时长
>12 weeks
期刊介绍: Archivum Immunologiae et Therapiae Experimentalis (AITE), founded in 1953 by Ludwik Hirszfeld, is a bimonthly, multidisciplinary journal. It publishes reviews and full original papers dealing with immunology, experimental therapy, immunogenetics, transplantation, microbiology, immunochemistry and ethics in science.
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