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Disrupting tumour vasculature and recruitment of aPDL1-loaded platelets control tumour metastasis

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Listed:
  • Hongjun Li

    (Zhejiang University
    Sir Run Run Shaw Hospital
    University of California
    University of California)

  • Zejun Wang

    (University of California
    University of California
    University of California)

  • Zhaowei Chen

    (Zhejiang University
    University of California
    Fuzhou University)

  • Tianyuan Ci

    (University of California)

  • Guojun Chen

    (University of California
    University of California
    University of California)

  • Di Wen

    (University of California
    University of California
    University of California)

  • Ruoxin Li

    (University of California
    University of California)

  • Jinqiang Wang

    (Zhejiang University
    University of California
    University of California
    University of California)

  • Huan Meng

    (University of California)

  • R. Bryan Bell

    (Earle A. Chiles Research Institute in the Robert W. Franz Cancer Center, Providence Cancer Institute)

  • Zhifeng Gu

    (Research Center of Clinical Medicine, Affiliated Hospital of Nantong University)

  • Gianpietro Dotti

    (Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University)

  • Zhen Gu

    (Zhejiang University
    Sir Run Run Shaw Hospital
    University of California
    University of California)

Abstract

Although therapies of cancer are advancing, it remains challenging for therapeutics to reach the sites of metastasis, which accounts for majority of cancer associated death. In this study, we have developed a strategy that guides an anti-programmed cell death-ligand 1 (aPDL1) antibody to accumulate in metastatic lesions to promote anti-tumour immune responses. Briefly, we have developed a combination in which Vadimezan disrupts tumour blood vessels of tumour metastases and facilitates the recruitment and activation of adoptively transferred aPDL1-conjugated platelets. In situ activated platelets generate aPDL1-decorated platelet-derived microparticles (PMP) that diffuse within the tumour and elicit immune responses. The proposed combination increases 10-fold aPDL1 antibody accumulation in lung metastases as compared to the intravenous administration of the antibody and enhances the magnitude of immune responses leading to improved antitumour effects.

Suggested Citation

  • Hongjun Li & Zejun Wang & Zhaowei Chen & Tianyuan Ci & Guojun Chen & Di Wen & Ruoxin Li & Jinqiang Wang & Huan Meng & R. Bryan Bell & Zhifeng Gu & Gianpietro Dotti & Zhen Gu, 2021. "Disrupting tumour vasculature and recruitment of aPDL1-loaded platelets control tumour metastasis," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22674-3
    DOI: 10.1038/s41467-021-22674-3
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