PD-1 Blockade Cellular Vesicles for Cancer Immunotherapy

Xudong Zhang, Chao Wang, Jinqiang Wang, Quanyin Hu, Benjamin Langworthy, Yanqi Ye, Wujin Sun, Jing Lin, Tianfu Wang, Jason Fine, Hao Cheng, Gianpietro Dotti, Peng Huang, Zhen Gu

Research output: Contribution to journalArticlepeer-review

230 Scopus citations

Abstract

Cancer cells resist to the host immune antitumor response via multiple suppressive mechanisms, including the overexpression of PD-L1 that exhausts antigen-specific CD8+ T cells through PD-1 receptors. Checkpoint blockade antibodies against PD-1 or PD-L1 have shown unprecedented clinical responses. However, limited host response rate underlines the need to develop alternative engineering approaches. Here, engineered cellular nanovesicles (NVs) presenting PD-1 receptors on their membranes, which enhance antitumor responses by disrupting the PD-1/PD-L1 immune inhibitory axis, are reported. PD-1 NVs exhibit a long circulation and can bind to the PD-L1 on melanoma cancer cells. Furthermore, 1-methyl-tryptophan, an inhibitor of indoleamine 2,3-dioxygenase can be loaded into the PD-1 NVs to synergistically disrupt another immune tolerance pathway in the tumor microenvironment. Additionally, PD-1 NVs remarkably increase the density of CD8+ tumor infiltrating lymphocytes in the tumor margin, which directly drive tumor regression.

Original languageEnglish (US)
Article number1707112
JournalAdvanced Materials
Volume30
Issue number22
DOIs
StatePublished - May 29 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

  • cancer immunotherapy
  • cell therapy
  • drug delivery
  • immune checkpoint blockade
  • nanomedicine

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