Injectable Bioresponsive Gel Depot for Enhanced Immune Checkpoint Blockade

Although cancer immunotherapy based on immune checkpoint inhibitors holds great promise toward many types of cancers, several challenges still remain, associated with low objective response of patient rate as well as systemic side effects. Here, a combination immunotherapy strategy is developed base...

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Bibliographic Details
Published in:Advanced materials (Weinheim) 2018-07, Vol.30 (28), p.e1801527-n/a
Main Authors: Yu, Shuangjiang, Wang, Chao, Yu, Jicheng, Wang, Jinqiang, Lu, Yue, Zhang, Yuqi, Zhang, Xudong, Hu, Quanyin, Sun, Wujin, He, Chaoliang, Chen, Xuesi, Gu, Zhen
Format: Article
Language:English
Subjects:
Cell death
checkpoint blockade
drug delivery
Gels
Humans
hydrogel
Immunotherapy
Materials science
Melanoma
Side effects
stimuli responsive
Sustained release
Tryptophan
Tumor Microenvironment
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Summary:Although cancer immunotherapy based on immune checkpoint inhibitors holds great promise toward many types of cancers, several challenges still remain, associated with low objective response of patient rate as well as systemic side effects. Here, a combination immunotherapy strategy is developed based on a thermogelling reactive oxygen species (ROS)‐responsive polypeptide gel for sustained release of anti‐programmed cell death‐ligand 1 antibody and dextro‐1‐methyl tryptophan, inhibitor of indoleamine‐2,3‐dioxygenase with leveraging the ROS level in the tumor microenvironment. This bioresponsive gel depot can effectively reduce the local ROS level and facilitate release of immunotherapeutics, which leads to enhanced anti‐melanoma efficacy in vivo. A bioresponsive polypeptide‐based gel depot is prepared for sustained release of anti‐programmed cell death‐ligand 1 antibody and dextro‐1‐methyl tryptophan (D‐1MT), inhibitor of indoleamine‐2,3‐dioxygenase with leveraging the reactive oxygen species level in the tumor microenvironment. This new combination immunotherapy strategy leads to significantly enhanced anti‐melanoma efficacy in vivo.
ISSN:0935-9648
1521-4095
DOI:10.1002/adma.201801527