肿瘤细胞治疗研究
英文原题：iPSC-derived T cells and macrophages: Manufacturing and next-generation application approaches.
嵌合抗原受体（CAR）技术已改变免疫治疗领域，在血液系统疾病治疗中取得重大成功。
嵌合抗原受体（CAR）技术凭借治疗血液系统疾病的显著成功，改变了免疫治疗领域。然而，规模化生产、供者差异及实体瘤治疗方面的挑战仍需创新解决方案。诱导多能干细胞（iPSC）技术作为CAR疗法的新兴可再生细胞来源，推动了现货型免疫细胞产品开发。本综述聚焦iPSC来源CAR-T细胞和CAR巨噬细胞的近期进展，包括分化方案、基因工程策略、减轻移植物抗宿主病（GVHD）的方法，以及克服组织相容性限制的替代策略。此外，我们讨论iPSC衍生技术如何提高低频免疫细胞群体的可及性，包括MR1限制性T细胞、γδT细胞、自然杀伤T（NKT）细胞和小胶质细胞。尽管已取得巨大进展，但临床经验仍有限、制造挑战仍存，需进一步探索。制造规模化和基因工程进展，使iPSC疗法处于临床策略前沿，有望应对癌症治疗尚未满足的临床需求。
Chimeric antigen receptor (CAR) technology has transformed the immunotherapy field with significant success in the treatment of hematological diseases. Nonetheless, challenges in scalability, donor variability as well as in the treatment of solid tumors warrants innovative solutions. Induced pluripotent stem cell (iPSC) technology has revolutionized the filed as an emerging renewable source for CAR-based therapies, facilitating the development of off-the-shelf immune cells products. This review focuses on the recent developments of iPSC-derived CAR-T cells and CAR-macrophages, including differentiation protocols, gene engineering strategies and mitigation of Graft-versus-Host Disease (GvHD), as well as alternatives for histocompatibility constraints. Additionally, we will discuss how iPSC-derivation enhances accessibility of low-frequency immune cell populations including MR1-restricted T, T, Natural Killer T (NKT) and Microglial cells. Despite great progress achieved, the limited but continuously growing clinical experience and manufacturing challenges, warrant further exploration. Advancements in manufacturing scalability and genetic engineering position iPSC-based therapies at the forefront of clinical strategies to address unmet clinical needs in cancer treatment.
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