Nianias Alexandros, Themeli Maria
Department of Hematology, Amsterdam University Medical Centers, Cancer Center Amsterdam, Location VUmc, Amsterdam, Netherlands.
Curr Hematol Malig Rep. 2019 Aug;14(4):261-268. doi: 10.1007/s11899-019-00528-6.
In the rapidly developing field of adoptive cell immunotherapy, there is urgent need for discoveries that would improve outcomes, extend the applicability, and reduce the costs. Induced pluripotent stem cells (iPSC) can be a source of broadly applicable cellular immunotherapeutics, which have been manufactured, validated, and banked in advance, and can be applied across HLA barriers. Here, we discuss the recent advances and challenges in the generation of iPSC-derived cellular products for cancer therapy.
iPSCs can be differentiated to functional tumor-specific T and NK cells in vitro with demonstrable in vitro and in vivo anti-tumor activity. Genetic modifications employed at the iPSC level can deliver desirable immunotherapeutic attributes to the generated immune effectors. iPSC-NK cells are currently evaluated in a clinical setting and pre-clinical testing of iPSC-T cells shows promising results but their production seems more challenging. The use of iPSCs for the generation of tumor-targeting T/NK cells constitutes a feasible strategy to overcome limitations in manufacturing, efficacy, and applicability of cellular therapeutics.
在快速发展的过继性细胞免疫治疗领域,迫切需要能改善治疗效果、扩大适用性并降低成本的新发现。诱导多能干细胞(iPSC)可成为广泛适用的细胞免疫治疗药物的来源,这些药物可预先制备、验证并储存,且能跨越人类白细胞抗原(HLA)屏障应用。在此,我们讨论用于癌症治疗的iPSC衍生细胞产品生成方面的最新进展和挑战。
iPSC可在体外分化为具有功能的肿瘤特异性T细胞和自然杀伤(NK)细胞,在体外和体内均具有可证实的抗肿瘤活性。在iPSC水平进行的基因改造可为所产生的免疫效应细胞赋予理想的免疫治疗特性。iPSC-NK细胞目前正在临床环境中进行评估,iPSC-T细胞的临床前测试显示出有希望的结果,但其生产似乎更具挑战性。使用iPSC生成肿瘤靶向性T/NK细胞是克服细胞治疗在制造、疗效和适用性方面局限性的可行策略。