Pluripotent stem cell-derived CAR-macrophage cells with antigen-dependent anti-cancer cell functions
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LETTER TO THE EDITOR
Open Access
Pluripotent stem cell‑derived CAR‑macrophage cells with antigen‑dependent anti‑cancer cell functions Li Zhang1,2†, Lin Tian1,2†, Xiaoyang Dai3†, Hua Yu1,2†, Jiajia Wang3†, Anhua Lei1,2, Mengmeng Zhu1,2, Jianpo Xu1,2, Wei Zhao1,2, Yuqing Zhu1,2, Zhen Sun1,2, Hao Zhang2,4, Yongxian Hu2,4, Yanlin Wang5, Yuming Xu5, George M. Church6, He Huang2,4,7*, Qinjie Weng3* and Jin Zhang1,2,7*
Abstract The Chimera antigen receptor (CAR)-T cell therapy has gained great success in the clinic. However, there are still major challenges for its wider applications in a variety of cancer types including lack of effectiveness due to the highly complex tumor microenvironment, and the forbiddingly high cost due to the personalized manufacturing procedures. In order to overcome these hurdles, numerous efforts have been spent focusing on optimizing Chimera antigen receptors, engineering and improving T cell capacity, exploiting features of subsets of T cell or NK cells, or making off-theshelf universal cells. Here, we developed induced pluripotent stem cells (iPSCs)-derived, CAR-expressing macrophage cells (CAR-iMac). CAR expression confers antigen-dependent macrophage functions such as expression and secretion of cytokines, polarization toward the pro-inflammatory/anti-tumor state, enhanced phagocytosis of tumor cells, and in vivo anticancer cell activity. This technology platform for the first time provides an unlimited source of iPSC-derived engineered CAR-macrophage cells which could be utilized to eliminate cancer cells. Keywords: Chimera antigen receptor (CAR), Induced pluripotent stem cells (iPSC)-derived macrophage cells (iMac), Antigen-dependent activation, Anti-cancer cell functions To the Editor, Recently, CAR-iPSC-differentiated CAR-expressing T cells and NK cells have been reported to have potent cytotoxic activity against cancer cells, and they represent a new family of engineered stem cell-derived immune *Correspondence: [email protected]; [email protected]; [email protected] † Li Zhang, Lin Tian, Xiaoyang Dai, Hua Yu and Jiajia Wang have contributed equally to this work 1 Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China 2 Institute of Hematology, Zhejiang University, Hangzhou 310058, China 3 Zhejiang Province Key Laboratory of Anti‑Cancer Drug Research, Center for Drug Safety Evaluation and Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China Full list of author information is available at the end of the article
cells for CAR therapies [1, 2]. Myeloid cells such as macrophages have been utilized as a type of effector cells to combat cancer cells by means of their phagocytosis function [3, 4]. However, immortalized macrophage cell lines are not applicable to clinical settings, and bone marrow or PBMC-derived primary macrophages are not efficiently engineered, thus leaving iP
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