Engineering the next generation of allogeneic CAR cells: iPSCs as a scalable and editable platform

作者：Ying Fang, Yuning Chen, Yan-Ruide Li · 发表于：Stem Cell Reports · 年份：2025 · DOI：10.1016/j.stemcr.2025.102515 · 被引用次数：23 · 研究领域：CRISPR and Genetic Engineering、CAR-T cell therapy research、Pluripotent Stem Cells Research

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.