Title

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

Authors

Hongjun Li
Zejun Wang
Zhaowei Chen
Tianyuan Ci
Guojun Chen
Di Wen
Ruoxin Li
Jinqiang Wang
Huan Meng
R Bryan Bell, Earle A. Chiles Research Institute in the Robert W. Franz Cancer Center, Providence Cancer Institute, Portland, OR, USAFollow
Zhifeng Gu
Gianpietro Dotti
Zhen Gu

Document Type

Article

Publication Date

5-13-2021

Publication Title

Nat Commun

Keywords

oregon; chiles

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.

Clinical Institute

Cancer

Department

Earle A. Chiles Research Institute

Department

Oncology

Recommended Citation

Li, Hongjun; Wang, Zejun; Chen, Zhaowei; Ci, Tianyuan; Chen, Guojun; Wen, Di; Li, Ruoxin; Wang, Jinqiang; Meng, Huan; Bryan Bell, R; Gu, Zhifeng; Dotti, Gianpietro; and Gu, Zhen, "Disrupting tumour vasculature and recruitment of aPDL1-loaded platelets control tumour metastasis." (2021). Articles, Abstracts, and Reports. 4959.
https://digitalcommons.providence.org/publications/4959