The KG Jebsen Center for Cancer Immunotherapy, University of Oslo, Oslo, Norway.
Department of Medicine, Huddinge, Karolinska Institute, Solna, Sweden.
Semin Immunopathol. 2019 Jan;41(1):59-68. doi: 10.1007/s00281-018-0721-x. Epub 2018 Oct 25.
Cell therapy is emerging as a very promising therapeutic modality against cancer, spearheaded by the clinical success of chimeric antigen receptor (CAR) modified T cells for B cell malignancies. Currently, FDA-approved CAR-T cell products are based on engineering of autologous T cells harvested from the patient, typically using a central manufacturing facility for gene editing before the product can be delivered to the clinic and infused to the patients. For a broader implementation of advanced cell therapy and to reduce costs, it would be advantageous to use allogeneic "universal" cell therapy products that can be stored in cell banks and provided upon request, in a manner analogous to biopharmaceutical drug products. In this review, we outline a roadmap for development of off-the-shelf cell therapy based on natural killer (NK) cells derived from induced pluripotent stem cells (iPSCs). We discuss strategies to engineer iPSC-derived NK (iPSC-NK) cells for enhanced functional potential, persistence, and homing.
细胞疗法作为一种很有前途的癌症治疗方法正在兴起，嵌合抗原受体 (CAR) 修饰的 T 细胞在治疗 B 细胞恶性肿瘤方面取得了临床成功，引领了这一领域的发展。目前，FDA 批准的 CAR-T 细胞产品基于从患者中采集的自体 T 细胞的工程改造，通常在产品能够交付给临床并输注给患者之前，在中央制造设施中进行基因编辑。为了更广泛地实施先进的细胞疗法并降低成本，使用可以存储在细胞库中并根据需要提供的同种异体“通用”细胞疗法产品将是有利的，其方式类似于生物制药产品。在这篇综述中，我们概述了基于诱导多能干细胞 (iPSC) 衍生的自然杀伤 (NK) 细胞的现成细胞疗法的开发路线图。我们讨论了用于增强功能潜力、持久性和归巢能力的工程 iPSC 衍生 NK(iPSC-NK) 细胞的策略。
