Abstract |
Patients with low-immunogenic tumors respond poorly to immune checkpoint blockade (ICB) targeting the programmed death-1 (PD-1)/ programmed death-ligand 1 (PD-L1) pathway. Conversely, patients responding to ICB can experience various side effects. We have thus engineered a therapeutic scaffold that, when formed in situ, allows the local release of gemcitabine (GEM) and an anti-PD-L1 blocking antibody (aPDL1) with distinct release kinetics. The scaffold consists of reactive oxygen species (ROS)-degradable hydrogel that releases therapeutics in a programmed manner within the tumor microenvironment (TME), which contains abundant ROS. We found that the aPDL1-GEM scaffold elicits an immunogenic tumor phenotype and promotes an immune-mediated tumor regression in the tumor-bearing mice, with prevention of tumor recurrence after primary resection.
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Authors | Chao Wang, Jinqiang Wang, Xudong Zhang, Shuangjiang Yu, Di Wen, Quanyin Hu, Yanqi Ye, Hunter Bomba, Xiuli Hu, Zhuang Liu, Gianpietro Dotti, Zhen Gu |
Journal | Science translational medicine
(Sci Transl Med)
Vol. 10
Issue 429
(02 21 2018)
ISSN: 1946-6242 [Electronic] United States |
PMID | 29467299
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. |
Chemical References |
- Programmed Cell Death 1 Receptor
- Deoxycytidine
- Hydrogel, Polyethylene Glycol Dimethacrylate
- Gemcitabine
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Topics |
- Animals
- Cell Line, Tumor
- Combined Modality Therapy
- Deoxycytidine
(analogs & derivatives, therapeutic use)
- Female
- Hydrogel, Polyethylene Glycol Dimethacrylate
(chemistry)
- Immunotherapy
(methods)
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Programmed Cell Death 1 Receptor
(metabolism)
- Gemcitabine
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