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.
Institute of Hematology, Zhejiang University, Hangzhou, 310058, China.
J Hematol Oncol. 2020 Nov 11;13(1):153. doi: 10.1186/s13045-020-00983-2.
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-the-shelf 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.
嵌合抗原受体 (CAR)-T 细胞疗法在临床上取得了巨大成功。然而，由于高度复杂的肿瘤微环境，其在包括多种癌症类型中的广泛应用仍存在重大挑战，并且由于个性化制造程序，成本高得令人望而却步。为了克服这些障碍，人们付出了大量努力来专注于优化嵌合抗原受体、工程和提高 T 细胞的能力、利用 T 细胞或 NK 细胞亚群的特征，或制造现成的通用细胞。在这里，我们开发了诱导多能干细胞 (iPSC) 衍生的、表达嵌合抗原受体的巨噬细胞 (CAR-iMac)。CAR 表达赋予巨噬细胞依赖抗原的功能，如细胞因子的表达和分泌、向促炎/抗肿瘤状态极化、增强对肿瘤细胞的吞噬作用以及体内抗癌细胞活性。这项技术平台首次提供了无限来源的 iPSC 衍生的工程 CAR-巨噬细胞，可用于消除癌细胞。
