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

Li Zhang1,2, Lin Tian1,2, Xiaoyang Dai3

  • 1Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.

Journal of Hematology & Oncology
|November 12, 2020
PubMed

Insights

Engineered macrophages derived from induced pluripotent stem cells (iPSCs) offer a novel approach to cancer therapy. These CAR-macrophage cells demonstrate potent anti-tumor activity, overcoming limitations of current CAR-T cell therapies.

Area of Science:

  • Immunology
  • Cell Biology
  • Biotechnology

Background:

  • CAR-T cell therapy shows clinical success but faces challenges like tumor microenvironment complexity and high manufacturing costs.
  • Existing strategies focus on optimizing CARs, T cell engineering, or using universal cells for broader application.

Discussion:

  • This study introduces induced pluripotent stem cells (iPSCs)-derived CAR-expressing macrophage cells (CAR-iMac) as a new therapeutic platform.
  • CAR expression enhances macrophage functions, including cytokine secretion, pro-inflammatory polarization, and phagocytosis of tumor cells.
  • CAR-iMacs exhibit in vivo anticancer cell activity, demonstrating their therapeutic potential.

Key Insights:

  • Development of an unlimited source of iPSC-derived engineered CAR-macrophage cells.
  • Demonstration of antigen-dependent, enhanced anti-tumor functions in CAR-macrophages.
  • Potential to overcome limitations of current CAR-based immunotherapies.

Outlook:

  • This platform offers a promising avenue for developing 'off-the-shelf' allogeneic cell therapies.
  • Further research could lead to more effective and accessible cancer treatments.
  • Potential for broader application across various cancer types by overcoming TME challenges.
Keywords:
Anti-cancer cell functionsAntigen-dependent activationChimera antigen receptor (CAR)Induced pluripotent stem cells (iPSC)-derived macrophage cells (iMac)

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