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

Publication date: Dec 20, 2019

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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Zhu, Y., Hu, X., Feng, L., Yang, Z., Zhou, L., Duan, X., Cheng, S., Zhang, W., Liu, B., and Zhang, K. Enhanced Therapeutic Efficacy of a Novel Oncolytic Herpes Simplex Virus Type 2 Encoding an Antibody Against Programmed Cell Death 1. 25194. 2019 Mol Ther Oncolytics (15):

Concepts Keywords
Blockade Biotechnology
Combinatorial Oncolytic virus
Eukaryotic Experimental cancer treatments
Herpes Simplex Virus Virotherapy
Immune Checkpoint Blockade Viruses
Immune System Clinical medicine
Immunogenic Immune system
Inhibitor Medicine
Melanoma Poorly immunogenic melanoma
Monoclonal Antibody Oncolytic herpes
Oncolytic Immunologically cold tumors
Oncolytic Virus Herpes simplex virus
Oncolytic Viruses Tumor microenvironment
Virus Checkpoint inhibitor

Semantics

Type Source Name
disease MESH tumors
disease MESH melanoma
pathway KEGG Melanoma

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