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Oncolytic Virus Encoding a Master Pro-Inflammatory Cytokine Interleukin 12 in Cancer Immunotherapy

Department of Immunotherapeutics and Biotechnology, Texas Tech University Health Sciences Center School of Pharmacy, Abilene, TX 79601, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(2), 400; https://doi.org/10.3390/cells9020400 (registering DOI)
Received: 21 December 2019 / Revised: 25 January 2020 / Accepted: 29 January 2020 / Published: 10 February 2020
(This article belongs to the Special Issue Cell Biology of Viral Infections)
Oncolytic viruses (OVs) are genetically modified or naturally occurring viruses, which preferentially replicate in and kill cancer cells while sparing healthy cells, and induce anti-tumor immunity. OV-induced tumor immunity can be enhanced through viral expression of anti-tumor cytokines such as interleukin 12 (IL-12). IL-12 is a potent anti-cancer agent that promotes T-helper 1 (Th1) differentiation, facilitates T-cell-mediated killing of cancer cells, and inhibits tumor angiogenesis. Despite success in preclinical models, systemic IL-12 therapy is associated with significant toxicity in humans. Therefore, to utilize the therapeutic potential of IL-12 in OV-based cancer therapy, 25 different IL-12 expressing OVs (OV-IL12s) have been genetically engineered for local IL-12 production and tested preclinically in various cancer models. Among OV-IL12s, oncolytic herpes simplex virus encoding IL-12 (OHSV-IL12) is the furthest along in the clinic. IL-12 expression locally in the tumors avoids systemic toxicity while inducing an efficient anti-tumor immunity and synergizes with anti-angiogenic drugs or immunomodulators without compromising safety. Despite the rapidly rising interest, there are no current reviews on OV-IL12s that exploit their potential efficacy and safety to translate into human subjects. In this article, we will discuss safety, tumor-specificity, and anti-tumor immune/anti-angiogenic effects of OHSV-IL12 as mono- and combination-therapies. In addition to OHSV-IL12 viruses, we will also review other IL-12-expressing OVs and their application in cancer therapy. View Full-Text
Keywords: cancer immunotherapy; oncolytic virus; herpes simplex virus; immune checkpoint inhibitor; angiogenesis inhibitor cancer immunotherapy; oncolytic virus; herpes simplex virus; immune checkpoint inhibitor; angiogenesis inhibitor
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MDPI and ACS Style

Nguyen, H.-M.; Guz-Montgomery, K.; Saha, D. Oncolytic Virus Encoding a Master Pro-Inflammatory Cytokine Interleukin 12 in Cancer Immunotherapy. Cells 2020, 9, 400.

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