期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 10, 期 429, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aan3682
关键词
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资金
- Alfred P. Sloan Foundation
- North Carolina Translational and Clinical Sciences Institute
- NIH Clinical and Translational Science Awards at UNC-CH [1L1TR001111]
- UNC Cancer Center
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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