Prospects for Development of Induced Pluripotent Stem Cell-Derived CAR-Targeted Immunotherapies.
Prospects for Development of Induced Pluripotent Stem Cell-Derived CAR-Targeted Immunotherapies.
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DOI：
10.1007/s00005-021-00640-7
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发表时间：
2021-12-12
影响因子：
3.2
通讯作者：
Maher J
中科院分区：
文献类型：
--
作者：
Mazza R;Maher J
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动力。与此同时，免疫疗法终于成为一种具有临床意义的癌症治疗方式。特别地，使用工程化以表达嵌合抗原受体（汽车）的离体扩增的自体T细胞，在患有选定的血液恶性肿瘤的患者中已经实现了令人印象深刻的功效。虽然实体瘤占人类癌症的90%以上，但目前这种治疗方法在很大程度上难以治愈。尽管如此，鉴于全球范围内CAR领域的大量创新，在不久的将来可能会出现针对常见实体瘤的有效解决方案。这种发展将在这些复杂、昂贵和个性化治疗的可扩展交付方面带来重大的新挑战。来源于iPSC的CAR工程化免疫细胞产品提供了产生无限数量的同质、标准化细胞产品的潜力，其中引入了多个定义的基因修饰事件，以确保安全性、效力和再现性。在这里，我们回顾了一些用于工程化表达CAR的iPSC衍生药物产品的新兴策略。
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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DOI：
10.1126/science.aao0505
发表时间：
2018-03-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ferrari de Andrade L;Tay RE;Pan D;Luoma AM;Ito Y;Badrinath S;Tsoucas D;Franz B;May KF Jr;Harvey CJ;Kobold S;Pyrdol JW;Yoon C;Yuan GC;Hodi FS;Dranoff G;Wucherpfennig KW
通讯作者：
Wucherpfennig KW
影响因子：
64.8
作者：
Eyquem J;Mansilla-Soto J;Giavridis T;van der Stegen SJ;Hamieh M;Cunanan KM;Odak A;Gönen M;Sadelain M
通讯作者：
Sadelain M
影响因子：
6
作者：
Arias J;Yu J;Varshney M;Inzunza J;Nalvarte I
通讯作者：
Nalvarte I
影响因子：
2.2
作者：
Bonk, Sarah;Tasdelen, Pinar;Weideman, Soeren A.
通讯作者：
Weideman, Soeren A.
影响因子：
15.3
作者：
Garbe, Annette I.;Krueger, Andreas;von Boehmer, Harald
通讯作者：
von Boehmer, Harald