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

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...

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Autores principales: 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, Gu, Zhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119987/
https://www.ncbi.nlm.nih.gov/pubmed/33986264
http://dx.doi.org/10.1038/s41467-021-22674-3
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author 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
Gu, Zhen
author_facet 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
Gu, Zhen
author_sort Li, Hongjun
collection PubMed
description 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.
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spelling pubmed-81199872021-05-18 Disrupting tumour vasculature and recruitment of aPDL1-loaded platelets control tumour metastasis 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 Gu, Zhen Nat Commun Article 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. Nature Publishing Group UK 2021-05-13 /pmc/articles/PMC8119987/ /pubmed/33986264 http://dx.doi.org/10.1038/s41467-021-22674-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
Gu, Zhen
Disrupting tumour vasculature and recruitment of aPDL1-loaded platelets control tumour metastasis
title Disrupting tumour vasculature and recruitment of aPDL1-loaded platelets control tumour metastasis
title_full Disrupting tumour vasculature and recruitment of aPDL1-loaded platelets control tumour metastasis
title_fullStr Disrupting tumour vasculature and recruitment of aPDL1-loaded platelets control tumour metastasis
title_full_unstemmed Disrupting tumour vasculature and recruitment of aPDL1-loaded platelets control tumour metastasis
title_short Disrupting tumour vasculature and recruitment of aPDL1-loaded platelets control tumour metastasis
title_sort disrupting tumour vasculature and recruitment of apdl1-loaded platelets control tumour metastasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119987/
https://www.ncbi.nlm.nih.gov/pubmed/33986264
http://dx.doi.org/10.1038/s41467-021-22674-3
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