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

Authors :
Li H
Wang Z
Chen Z
Ci T
Chen G
Wen D
Li R
Wang J
Meng H
Bryan Bell R
Gu Z
Dotti G
Gu Z
Source :
Nature communications [Nat Commun] 2021 May 13; Vol. 12 (1), pp. 2773. Date of Electronic Publication: 2021 May 13.
Publication Year :
2021

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.

Details

Language :
English
ISSN :
2041-1723
Volume :
12
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
33986264
Full Text :
https://doi.org/10.1038/s41467-021-22674-3