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Hybrid cellular membrane nanovesicles amplify macrophage immune responses against cancer recurrence and metastasis

Author

Listed:
  • Lang Rao

    (National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health)

  • Lei Wu

    (Wuhan University)

  • Zhida Liu

    (University of Texas Southwestern Medical Center)

  • Rui Tian

    (National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health
    Xiamen University)

  • Guocan Yu

    (National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health)

  • Zijian Zhou

    (National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health)

  • Kuikun Yang

    (National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health)

  • Hong-Gang Xiong

    (Wuhan University)

  • Anli Zhang

    (University of Texas Southwestern Medical Center)

  • Guang-Tao Yu

    (Wuhan University)

  • Wenjing Sun

    (Xiamen University)

  • Han Xu

    (Xiamen University)

  • Jingya Guo

    (Chinese Academy of Sciences Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences)

  • Andrew Li

    (Johns Hopkins University)

  • Hongmin Chen

    (Xiamen University)

  • Zhi-Jun Sun

    (Wuhan University)

  • Yang-Xin Fu

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Xiaoyuan Chen

    (National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health)

Abstract

Effectively activating macrophages against cancer is promising but challenging. In particular, cancer cells express CD47, a ‘don’t eat me’ signal that interacts with signal regulatory protein alpha (SIRPα) on macrophages to prevent phagocytosis. Also, cancer cells secrete stimulating factors, which polarize tumor-associated macrophages from an antitumor M1 phenotype to a tumorigenic M2 phenotype. Here, we report that hybrid cell membrane nanovesicles (known as hNVs) displaying SIRPα variants with significantly increased affinity to CD47 and containing M2-to-M1 repolarization signals can disable both mechanisms. The hNVs block CD47-SIRPα signaling axis while promoting M2-to-M1 repolarization within tumor microenvironment, significantly preventing both local recurrence and distant metastasis in malignant melanoma models. Furthermore, by loading a stimulator of interferon genes (STING) agonist, hNVs lead to potent tumor inhibition in a poorly immunogenic triple negative breast cancer model. hNVs are safe, stable, drug loadable, and suitable for genetic editing. These properties, combined with the capabilities inherited from source cells, make hNVs an attractive immunotherapy.

Suggested Citation

  • Lang Rao & Lei Wu & Zhida Liu & Rui Tian & Guocan Yu & Zijian Zhou & Kuikun Yang & Hong-Gang Xiong & Anli Zhang & Guang-Tao Yu & Wenjing Sun & Han Xu & Jingya Guo & Andrew Li & Hongmin Chen & Zhi-Jun , 2020. "Hybrid cellular membrane nanovesicles amplify macrophage immune responses against cancer recurrence and metastasis," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18626-y
    DOI: 10.1038/s41467-020-18626-y
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    Cited by:

    1. Ying Huang & Geng Qin & TingTing Cui & Chuanqi Zhao & Jinsong Ren & Xiaogang Qu, 2023. "A bimetallic nanoplatform for STING activation and CRISPR/Cas mediated depletion of the methionine transporter in cancer cells restores anti-tumor immune responses," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Yuxin Guo & Shao-Zhe Wang & Xinping Zhang & Hao-Ran Jia & Ya-Xuan Zhu & Xiaodong Zhang & Ge Gao & Yao-Wen Jiang & Chengcheng Li & Xiaokai Chen & Shun-Yu Wu & Yi Liu & Fu-Gen Wu, 2022. "In situ generation of micrometer-sized tumor cell-derived vesicles as autologous cancer vaccines for boosting systemic immune responses," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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