Generation of anti-GD2 CAR macrophages from human pluripotent stem cells for cancer immunotherapies

作者：Jue Zhang, Sarah Webster, Bret Duffin, Matthew N. Bernstein, John Steill, Scott Swanson, Matthew H. Forsberg, Jennifer M. Bolin, Matthew E. Brown, Aditi Majumder, Christian M. Capitini, Ron Stewart, James A. Thomson, Igor I. Slukvin · 发表于：Stem Cell Reports · 年份：2023 · DOI：10.1016/j.stemcr.2022.12.012 · 被引用次数：93 · 研究领域：CAR-T cell therapy research、Neuroblastoma Research and Treatments、Pluripotent Stem Cells Research

Macrophages armed with chimeric antigen receptors (CARs) provide a potent new option for treating solid tumors. However, genetic engineering and scalable production of somatic macrophages remains significant challenges. Here, we used CRISPR-Cas9 gene editing methods to integrate an anti-GD2 CAR into the AAVS1 locus of human pluripotent stem cells (hPSCs). We then established a serum- and feeder-free differentiation protocol for generating CAR macrophages (CAR-Ms) through arterial endothelial-to-hematopoietic transition (EHT). CAR-M produced by this method displayed a potent cytotoxic activity against GD2-expressing neuroblastoma and melanoma in vitro and neuroblastoma in vivo. This study provides a new platform for the efficient generation of off-the-shelf CAR-Ms for antitumor immunotherapy.