构建下一代同种异体嵌合抗原受体（CAR）细胞：诱导多能干细胞（iPSC）作为一个可扩展且可编辑的平台
Engineering the next generation of allogeneic CAR cells: iPSCs as a scalable and editable platform.
作者信息
Fang Ying, Chen Yuning, Li Yan-Ruide
机构信息
Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
出版信息
Stem Cell Reports. 2025 Jul 8;20(7):102515. doi: 10.1016/j.stemcr.2025.102515. Epub 2025 Jun 5.
Over the past five years, allogeneic off-the-shelf CAR-engineered cell therapies have advanced rapidly. By bypassing the individualized manufacturing, high cost, and eligibility constraints of autologous products, allogeneic platforms, especially those derived from induced pluripotent stem cells (iPSCs), promise broader, faster access for cancer patients. This perspective reviews recent preclinical and clinical milestones, outlining genetic designs, scalable production workflows, and early-phase trial outcomes. We assess safety profiles, antitumor activity, and in vivo persistence, spotlighting innovations like T cell receptor alpha constant (TRAC) knockout, human leukocyte antigen (HLA) camouflage, and interleukin (IL)-15 armoring. Finally, we identify emerging trends and challenges that will shape the future development of allogeneic iPSC-derived CAR therapies.
在过去五年中，现成的同种异体嵌合抗原受体（CAR）工程细胞疗法发展迅速。通过绕过自体产品的个体化制造、高成本和适用资格限制，同种异体平台，尤其是那些源自诱导多能干细胞（iPSC）的平台，有望为癌症患者提供更广泛、更快速的治疗途径。本文综述了近期的临床前和临床里程碑，概述了基因设计、可扩展的生产流程以及早期试验结果。我们评估了安全性、抗肿瘤活性和体内持久性，重点介绍了诸如T细胞受体α恒定区（TRAC）敲除、人类白细胞抗原（HLA）伪装和白细胞介素（IL）-15增强等创新技术。最后，我们确定了将塑造同种异体iPSC衍生CAR疗法未来发展的新兴趋势和挑战。
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