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Publication : Enhanced Therapeutic Efficacy of a Novel Oncolytic Herpes Simplex Virus Type 2 Encoding an Antibody Against Programmed Cell Death 1.

First Author  Zhu Y Year  2019
Journal  Mol Ther Oncolytics Volume  15
Pages  201-213 PubMed ID  31788554
Mgi Jnum  J:288057 Mgi Id  MGI:6415760
Doi  10.1016/j.omto.2019.10.003 Citation  Zhu Y, et al. (2019) Enhanced Therapeutic Efficacy of a Novel Oncolytic Herpes Simplex Virus Type 2 Encoding an Antibody Against Programmed Cell Death 1. Mol Ther Oncolytics 15:201-213
abstractText  The efficacy of immune checkpoint blockade therapy against immunologically "cold" tumors can be enhanced by applying the checkpoint inhibitors in combination with oncolytic viruses. Alternatively, the oncolytic virus construct has been modified to express factors that boost oncolytic virus function. We engineered a novel oncolytic herpes simplex virus 2 (HSV2) encoding an anti-human programmed cell death 1 (PD-1) monoclonal antibody (oHSV2-aPD1). This virus resulted in the detectable expression of a functional monoclonal antibody against human PD-1 by infecting eukaryotic cells. Therapeutic efficacy of oHSV2-aPD1 proved superior to unmodified oncolytic HSV2 treatment or PD-1 blockade alone and as effective as their combination in the poorly immunogenic melanoma models. Additionally, local oHSV2-aPD1 treatment induced a durable antitumor response and activated many immune effector cells and molecules both in the tumor microenvironment and in the systemic immune system. This provides support for combinatorial strategies involving local administration of an oncolytic HSV2 expressing a PD-1 inhibitor.
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