Abstract：
Cell-based immunotherapy, such as chimeric antigen receptor (CAR) T cell therapy, has revolutionized the treatment of hematological malignancies, especially in patients who are refractory to other therapies. However, there are critical obstacles that hinder the widespread clinical applications of current autologous therapies, such as high cost, challenging large-scale manufacturing, and inaccessibility to the therapy for lymphopenia patients. Therefore, it is in great demand to generate the universal off-the-shelf cell products with significant scalability. Human induced pluripotent stem cells (iPSCs) provide an \"unlimited supply\" for cell therapy because of their unique self-renewal properties and the capacity to be genetically engineered. iPSCs can be differentiated into different immune cells, such as T cells, natural killer (NK) cells, invariant natural killer T (iNKT) cells, gamma delta T (γδ T), mucosal-associated invariant T (MAIT) cells, and macrophages (Mφs). In this review, we describe iPSC-based allogeneic cell therapy, the different culture methods of generating iPSC-derived immune cells (e.g., iPSC-T, iPSC-NK, iPSC-iNKT, iPSC-γδT, iPSC-MAIT and iPSC-Mφ), as well as the recent advances in iPSC-T and iPSC-NK cell therapies, particularly in combinations with CAR-engineering. We also discuss the current challenges and the future perspectives in this field towards the foreseeable applications of iPSC-based immune therapy.
摘要：
基于细胞的免疫疗法，如嵌合抗原受体（CAR）T细胞疗法，彻底改变了血液恶性肿瘤的治疗方法，尤其是对其他疗法难以治疗的患者。然而,有严重的障碍阻碍了目前自体疗法的广泛临床应用，例如高成本，挑战大规模制造，以及淋巴细胞减少症患者无法接受治疗。因此,生成具有显著可扩展性的通用现成电池产品的需求很大。人类诱导多能干细胞（iPSCs）由于其独特的自我更新特性和基因工程能力，为细胞治疗提供了“无限供应”。iPSCs可以分化为不同的免疫细胞，比如T细胞,自然杀伤（NK）细胞，不变的自然杀伤T（iNKT）细胞，γδT(γδT),粘膜相关不变T（MAIT）细胞，和巨噬细胞（Mφs）。在这次审查中,我们描述了基于iPSC的同种异体细胞疗法，产生iPSC来源的免疫细胞的不同培养方法(例如，iPSC-T,iPSC-NK,iPSC-iNKT,iPSC-γδT,iPSC-MAIT和iPSC-Mφ)，以及iPSC-T和iPSC-NK细胞疗法的最新进展，特别是与汽车工程的组合。我们还讨论了基于iPSC的免疫疗法的可预见应用的当前挑战和该领域的未来前景。
