PD‐1 Blockade Cellular Vesicles for Cancer Immunotherapy

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. H...

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Bibliographic Details
Published in:Advanced materials (Weinheim) 2018-05, Vol.30 (22), p.e1707112-n/a
Main Authors: Zhang, Xudong, Wang, Chao, Wang, Jinqiang, Hu, Quanyin, Langworthy, Benjamin, Ye, Yanqi, Sun, Wujin, Lin, Jing, Wang, Tianfu, Fine, Jason, Cheng, Hao, Dotti, Gianpietro, Huang, Peng, Gu, Zhen
Format: Article
Language:English
Subjects:
Antibodies
Cancer
cancer immunotherapy
cell therapy
drug delivery
Humans
immune checkpoint blockade
Immunotherapy
Lymphocytes
Lymphocytes, Tumor-Infiltrating
Materials science
nanomedicine
Neoplasms - therapy
Programmed Cell Death 1 Receptor
Receptors
T-Lymphocytes
Tryptophan
Tumor Microenvironment
Tumors
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Summary: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. Cellular nanovesicles (NVs) presenting PD‐1 receptors on their membrane are genetically engineered for disturbing the PD1/PD‐L1 immune inhibitory axis. Additionally, 1‐methyl‐tryptophan (1‐MT), an inhibitor of indoleamine 2,3‐dioxygenase (IDO) can be loaded into the PD‐1 NVs to synergistically promote antitumor efficacy. This formulation provides a promising strategy that leverages functions of immune checkpoint blockade and encapsulated therapeutics for enhancing cancer immunotherapy.
ISSN:0935-9648
1521-4095
DOI:10.1002/adma.201707112