Pluripotent stem cell-derived CAR-macrophage cells with antigen-dependent anti-cancer cell functions

  • J Hematol Oncol. 2020 Nov 11;13(1):153. doi: 10.1186/s13045-020-00983-2.
Li Zhang  1  2 ,  Lin Tian  1  2 ,  Xiaoyang Dai  3 ,  Hua Yu  1  2 ,  Jiajia Wang  3 ,  Anhua Lei  1  2 ,  Mengmeng Zhu  1  2 ,  Jianpo Xu  1  2 ,  Wei Zhao  1  2 ,  Yuqing Zhu  1  2 ,  Zhen Sun  1  2 ,  Hao Zhang  2  4 ,  Yongxian Hu  2  4 ,  Yanlin Wang  5 ,  Yuming Xu  5 ,  George M Church  6 ,  He Huang  7  8  9 ,  Qinjie Weng  10 ,  Jin Zhang  11  12  13
Affiliations
  • 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.
  • 4. The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.
  • 5. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
  • 6. Department of Genetics and Wyss Institute for Biologically Inspired Engineering, Harvard Medical School, Boston, MA, 02115, USA.
  • 7. Institute of Hematology, Zhejiang University, Hangzhou, 310058, China. [email protected].
  • 8. The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China. [email protected].
  • 9. Zhejiang Laboratory for Systems and Precision Medicine, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, 311121, China. [email protected].
  • 10. 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. [email protected].
  • 11. 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. [email protected].
  • 12. Institute of Hematology, Zhejiang University, Hangzhou, 310058, China. [email protected].
  • 13. Zhejiang Laboratory for Systems and Precision Medicine, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, 311121, China. [email protected].
PMID: 33176869 DOI: 10.1186/s13045-020-00983-2
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-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.

Keywords
Anti-cancer cell functions; Antigen-dependent activation; Chimera antigen receptor (CAR); Induced pluripotent stem cells (iPSC)-derived macrophage cells (iMac).