Oncolytic Poxviruses

Abstract

Current standard treatments of cancer can prolong survival of many cancer patients but usually do not effectively cure the disease. Oncolytic virotherapy is an emerging therapeutic for the treatment of cancer that exploits replication-competent viruses to selectively infect and destroy cancerous cells while sparing normal cells and tissues. Clinical and/or preclinical studies on oncolytic viruses have revealed that the candidate viruses being tested in trials are remarkably safe and offer potential for treating many classes of currently incurable cancers. Among these candidates are vaccinia and myxoma viruses, which belong to the family Poxviridae and possess promising oncolytic features. This article describes poxviruses that are being developed for oncolytic virotherapy and summarizes the outcomes of both clinical and preclinical studies. Additionally, studies demonstrating superior efficacy when poxvirus oncolytic virotherapy is combined with conventional therapies are described.

Vectorization in an oncolytic vaccinia virus of an antibody, a Fab and a scFv against programmed cell death -1 (PD-1) allows their intratumoral delivery and an improved tumor-growth inhibition

“…Oncolytic vaccinia viruses can also be modified to express a transgene (armed virus) that either increases their safety profile or enhances their oncolytic efficiency 4 . For example, TG6002 is a double deleted thymidine kinase (TK-) , ribonucleotide reductase ( RR- ) Copenhagen vaccinia virus strain encoding an enzyme (FCU1) that transform the anti-fungal prodrug 5-fluorocytosine (5-FC) into the cytotoxic 5-Fluorouracil (5-FU) 5 .…”

Oncolytic Virotherapy: A Brief Overview

“…The inverse is true in cancer cells [8,9]. This selectivity, in the case of the thymidine knockouts, is present because normal cells that are not undergoing rapid division will not have an excess of thymidine or thymidine kinase and will therefore hinder viral replication long enough for the host to defend itself against infection [10]. Cancer cells, which are always mitotic, more often than not have an excess of thymidine which the virus can use to successfully replicate its genome [8].…”

Replicating poxviruses for human cancer therapy

“…SQPV was isolated from a grey squirrel (Sciurus carolinensis) in Maryland in 1953 and initially placed into the genus Leporipoxvirus by Kilham et al (1953); it was later thought to be a member of the genus Parapoxvirus (Housawi et al, 1998), but a sub- (Chen et al, 2001;Zhang et al, 2007;Kochneva et al, 2012;Chan and McFadden, 2014) Breast tumor model, Ovarian tumor model, etc (Hung et al, 2007;Zhang et al, 2007;Hiley et al, 2010;Gholami et al, 2014) Various solid tumors, Breast cancer (Gentschev et al, 2014;Mell et al, 2014) GLV-1h68*, GLV-1h99, GLV-1h108, VV-mIL2, VVhEA, VV-hup53, etc Wyeth Attenuated, transgenes inserted (Mastrangelo et al, 1999;Liu et al, 2014) Melanoma model, Bladder cancer model, etc (Mastrangelo et al, 1999;Gomella et al, 2001) Melanoma cancer, Liver cancer, etc (Mastrangelo et al, 1999;Park et al, 2008;Heo et al, 2013) JX-594* WR Attenuated, transgenes inserted (Gnant et al, 1999;McCart et al, 2001;Thorne et al, 2007;Parviainen et al, 2015) Colon cancer model. etc (Gnant et al, 1999;McCart et al, 2001;Autio et al, 2014) Various tumors (Zeh et al, 2015) JX-795, JX-963*, vvDD*, VV-TRAIL, etc MVA Severely attenuated, transgenes inserted (Sutter and Moss, 1992;Kochneva et al, 2012) Various cancer model (Drexler et al, 1999;Carroll et al, 1997) Various tumors (Larocca and Schlom, 2011;Amato et al, 2012;Gómez et al, 2013) MVA-5T4*, MVAhup53…”