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

破坏肿瘤血管系统和募集负载PDL1的血小板可控制肿瘤转移

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作者: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

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.

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