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dc.contributor.authorKloepper, Jonas
dc.contributor.authorRiedemann, Lars
dc.contributor.authorAmoozgar, Zohreh
dc.contributor.authorSeano, Giorgio
dc.contributor.authorSusek, Katharina
dc.contributor.authorYu, Veronica
dc.contributor.authorDalvie, Nisha
dc.contributor.authorAmelung, Robin
dc.contributor.authorDatta, Meenal
dc.contributor.authorSong, Jonathan
dc.contributor.authorAskoxylakis, Vasileios
dc.contributor.authorTaylor, Jennie
dc.contributor.authorLu-Emerson, Christine
dc.contributor.authorBatista, Ana
dc.contributor.authorKirkpatrick, Nathaniel
dc.contributor.authorJung, Keehoon
dc.contributor.authorSnuderl, Matija
dc.contributor.authorMuzikansky, Alona
dc.contributor.authorStubenrauch, Kay
dc.contributor.authorKrieter, Oliver
dc.contributor.authorWakimoto, Hiroaki
dc.contributor.authorXu, Lei
dc.contributor.authorMunn, Lance
dc.contributor.authorDuda, Dan
dc.contributor.authorFukumura, Dai
dc.contributor.authorBatchelor, Tracy
dc.contributor.authorJain, Rakesh
dc.date.accessioned2019-10-05T03:29:08Z
dc.date.issued2016
dc.identifier.citationKloepper, Jonas, Lars Riedemann, Zohreh Amoozgar, Giorgio Seano, Katharina Susek, Veronica Yu, Nisha Dalvie, et al. 2016. “Ang-2/VEGF Bispecific Antibody Reprograms Macrophages and Resident Microglia to Anti-Tumor Phenotype and Prolongs Glioblastoma Survival.” Proceedings of the National Academy of Sciences 113 (16): 4476–81. https://doi.org/10.1073/pnas.1525360113.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41483043*
dc.description.abstractInhibition of the vascular endothelial growth factor (VEGF) pathway has failed to improve overall survival of patients with glioblastoma (GBM). We previously showed that angiopoietin-2 (Ang-2) overexpression compromised the benefit from anti-VEGF therapy in a preclinical GBM model. Here we investigated whether dual Ang-2/VEGF inhibition could overcome resistance to anti-VEGF treatment. We treated mice bearing orthotopic syngeneic (Gl261) GBMs or human (MGG8) GBM xenografts with antibodies inhibiting VEGF (B20), or Ang-2/VEGF (CrossMab, A2V). We examined the effects of treatment on the tumor vasculature, immune cell populations, tumor growth, and survival in both the Gl261 and MGG8 tumor models. We found that in the Gl261 model, which displays a highly abnormal tumor vasculature, A2V decreased vessel density, delayed tumor growth, and prolonged survival compared with B20. In the MGG8 model, which displays a low degree of vessel abnormality, A2V induced no significant changes in the tumor vasculature but still prolonged survival. In both the Gl261 and MGG8 models A2V reprogrammed protumor M2 macrophages toward the antitumor M1 phenotype. Our findings indicate that A2V may prolong survival in mice with GBM by reprogramming the tumor immune microenvironment and delaying tumor growth.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleAng-2/VEGF bispecific antibody reprograms macrophages and resident microglia to anti-tumor phenotype and prolongs glioblastoma survival
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorDuda, Dan Gabriel::c98e9e279162984be65d72fd1be7bde2::600
dc.date.available2019-10-05T03:29:08Z
dash.workflow.comments1Science Serial ID 92292
dc.identifier.doi10.1073/pnas.1525360113
dash.source.volume113;16
dash.source.page4476


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