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In situ formed reactive oxygen species-responsive scaffold with gemcitabine and checkpoint inhibitor for combination therapy.

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.
AuthorsChao Wang, Jinqiang Wang, Xudong Zhang, Shuangjiang Yu, Di Wen, Quanyin Hu, Yanqi Ye, Hunter Bomba, Xiuli Hu, Zhuang Liu, Gianpietro Dotti, Zhen Gu
JournalScience translational medicine (Sci Transl Med) Vol. 10 Issue 429 (02 21 2018) ISSN: 1946-6242 [Electronic] United States
PMID29467299 (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.)
CopyrightCopyright © 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
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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