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; Zhen Gu

doi:10.1038/s41467-021-22674-3

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

Nat Commun. 2021 May 13;12(1):2773. doi: 10.1038/s41467-021-22674-3.

Authors

Hongjun Li^{1

2

3

4

5}, Zejun Wang^{3

4

5}, Zhaowei Chen^{1

3

6}, Tianyuan Ci³, Guojun Chen^{3

4

5}, Di Wen^{3

4

5}, Ruoxin Li^{3

5}, Jinqiang Wang^{1

3

4

5}, Huan Meng⁵, R Bryan Bell⁷, Zhifeng Gu⁸, Gianpietro Dotti⁹, Zhen Gu^{10

11

12

13

14}

Affiliations

¹ College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
² Zhejiang University Medical Center, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China.
³ Department of Bioengineering, University of California, Los Angeles, CA, USA.
⁴ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA.
⁵ California NanoSystems Institute, University of California, Los Angeles, CA, USA.
⁶ Institute of Food Safety and Environment Monitoring, College of Chemistry, Fuzhou University, Fuzhou, China.
⁷ Earle A. Chiles Research Institute in the Robert W. Franz Cancer Center, Providence Cancer Institute, Portland, OR, USA.
⁸ Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.
⁹ Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA.
¹⁰ College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China. guzhen@zju.edu.cn.
¹¹ Zhejiang University Medical Center, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China. guzhen@zju.edu.cn.
¹² Department of Bioengineering, University of California, Los Angeles, CA, USA. guzhen@zju.edu.cn.
¹³ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA. guzhen@zju.edu.cn.
¹⁴ California NanoSystems Institute, University of California, Los Angeles, CA, USA. guzhen@zju.edu.cn.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
B7-H1 Antigen / antagonists & inhibitors*
B7-H1 Antigen / immunology
Blood Platelets / metabolism*
Cell Line, Tumor
Female
Lung Neoplasms / drug therapy
Lung Neoplasms / pathology
Lung Neoplasms / secondary
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Neoplasm Metastasis / drug therapy
Neoplasm Metastasis / pathology
Neoplasms / blood supply*
Neoplasms / drug therapy*
Neoplasms / immunology
Neoplasms / pathology
Platelet Activation / drug effects
Platelet Transfusion
Xanthones / pharmacology*

Substances

Antineoplastic Agents
B7-H1 Antigen
Cd274 protein, mouse
Xanthones
vadimezan

Associated data

figshare/10.6084/m9.figshare.14099444.v1

Grants and funding

R01 CA234343/CA/NCI NIH HHS/United States