ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Stem Cell Research
This article is part of the Research TopiciPSC-derived Immune Cells: Revolutionizing Immunotherapy and Disease TreatmentView all articles
Activation of FCGR2A enhances the antitumor efficacy of hPSC-derived CAR-M
Provisionally accepted
- 1Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
- 2Chinese Academy of Sciences Stem Cell and Regenerative Medicine Innovation Institute, Beijing, China
- 3Institute of Biophysics Chinese Academy of Sciences, Chaoyang, China
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Chimeric antigen receptor macrophages (CAR-Ms) represent a novel approach in cellular immunotherapy. Human pluripotent stem cells (hPSCs) provide an unlimited and renewable cell source, enabling scalable and standardized production of CAR-Ms with consistent quality. In this study, we established a robust differentiation protocol to generate CAR-Ms from hPSCs. To evaluate HER2-directed hPSC-derived CAR-M functionality, we first profiled HER2 expression across multiple tumor cell lines and identified SKOV3 as the optimal target due to its high HER2 level. CAR constructs incorporating intracellular domains from CD3ε, FCGR1A, FCGR2A, FCGR2B, and FCGR3A were introduced into hPSCs via lentiviral transduction. Importantly, CAR expression did not impair hPSCs differentiation into macrophages. Functional assays revealed that all CAR-Ms exerted cytotoxic effects on HER2-positive SKOV3 cells, with FCGR2A-based CAR-Ms demonstrating the strongest activity. Furthermore, polarization of CAR-Ms into a proinflammatory state significantly enhanced tumor-killing efficacy, particularly in FCGR2A CAR-Ms. These findings highlight the potential of FCGR2A as an optimal signaling domain for CAR-M design and underscore the therapeutic promise of proinflammatory polarized CAR-Ms in solid tumor immunotherapy.
Keywords: Chimeric antigen receptor macrophages (CAR-Ms), FCGR2A, human pluripotent stemcells(hPSCs), Proinflammatorymacrophagepolarization, tumorimmunotherapy
Received: 16 Oct 2025; Accepted: 16 Dec 2025.
Copyright: © 2025 Yang, Li, Zhu, Li, Wang, Han and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Liuliu Yang
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