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Arming an oncolytic herpes simplex virus Type 1 with a single chain fragment variable antibody against PD-1 for experimental glioblastoma therapy.

Clin. Cancer Res.. 2018-10; 
PassaroCarmela,AlayoQuazim,DeLauraIsabel,McNultyJohn J,GrauwetKorneel,ItoHirotaka,BhaskaranVivek,MineoMarco,LawlerSean E,ShahKhalid,SperanzaMaria C,GoinsWilliam F,McLaughlinEric,FernandezSoledad,ReardonDavid A,FreemanGordon J,ChioccaE Antonio,NakashimaHir
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Peptide Synthesis … 152 DNA constructs and HSV packaging 153 pcDNA3-scFvPD-1: The scFvPD-1 cDNA encoding heavy and light chain variants of PD-1 154 antibody (clone 332.8H3, (16)) with 3x linker peptide (GGGGS) was synthesized in GenScript 155 and cloned in pcDNA3 (Invitrogen) … Get A Quote

摘要

Glioblastoma (GBM) is resistant to standard of care. Immune checkpoints inhibitors (such as anti-PD-1 monoclonal antibodies) efficiently restore anti-tumor T-cell activity. We engineered a new oncolytic herpes simplex virus (oHSV) expressing a single-chain antibody against PD-1 (scFvPD-1) to evaluate its efficacy in mouse models of GBM. Experimental plan: NG34scFvPD-1expresses the human GADD34 gene transcriptionally controlled by the Nestin promoter to allow replication in GBM cells and a scFvPD-1 cDNA transcriptionally controlled by the CMV promoter. ELISA assays were performed to detect binding of scFvPD-1 to mouse and human PD-1. In vitro cytotoxicity and replication assays were performed to measure NG34scFv... More

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