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

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 and Zhen Gu ()
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Hongjun Li: Zhejiang University
Zejun Wang: University of California
Zhaowei Chen: Zhejiang University
Tianyuan Ci: University of California
Guojun Chen: University of California
Di Wen: University of California
Ruoxin Li: University of California
Jinqiang Wang: Zhejiang University
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

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-22674-3

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