Oncolytic Virotherapy of Cancer

Chen, Nanhai G.; Szalay, Aladar A.

doi:10.1007/978-90-481-9704-0_16

Cited by 7 publications

(9 citation statements)

References 210 publications

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“…Additionally, safety is still a major concern in oncolytic viral therapy 30 . Hagen as well as Grigg e t al.…”

Section: Discussionmentioning

confidence: 99%

Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer Agent

Kirscher¹,

Deán‐Ben²,

Scadeng³

et al. 2015

Theranostics

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We reported earlier the diagnostic potential of a melanogenic vaccinia virus based system in magnetic resonance (MRI) and optoacoustic deep tissue imaging (MSOT). Since melanin overproduction lead to attenuated virus replication, we constructed a novel recombinant vaccinia virus strain (rVACV), GLV-1h462, which expressed the key enzyme of melanogenesis (tyrosinase) under the control of an inducible promoter-system. In this study melanin production was detected after exogenous addition of doxycycline in two different tumor xenograft mouse models. Furthermore, it was confirmed that this novel vaccinia virus strain still facilitated signal enhancement as detected by MRI and optoacoustic tomography. At the same time we demonstrated an enhanced oncolytic potential compared to the constitutively melanin synthesizing rVACV system.

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“…Additionally, safety is still a major concern in oncolytic viral therapy 30 . Hagen as well as Grigg e t al.…”

Section: Discussionmentioning

confidence: 99%

Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer Agent

Kirscher¹,

Deán‐Ben²,

Scadeng³

et al. 2015

Theranostics

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“…Following a series of disappointing clinical trials, interest in oncolytic viruses waned in the 1970–80s until the development of genetic engineering in the 1990s made it possible to alter viral genomes [ 18 ]. This technological advancement allowed manipulation of the viral genome to improve selectivity and decrease toxicity.…”

Section: Brief History Of Oncolytic Virusesmentioning

confidence: 99%

“…Restricting viral entry and infection through transductional targeting has been accomplished by several methods, including the use of adaptor molecules to facilitate binding of viral attachment proteins to a specific target cell’s receptor, pseudotyping with a different viral strain’s attachment protein, and genetically engineering viral expression of target ligands directed at specific tumor cells [ 18 ]. These strategies have been applied to increase the tumor selectivity of oncolytic adenoviruses, vaccinia virus (VACV), and measles virus [ 30 , 31 , 32 ].…”

Section: Mechanisms Of Tumor Selectivitymentioning

confidence: 99%

“…Finally, measures to prevent viral clearance and/or inactivation have been developed and recently demonstrated to enhance OV efficacy by prolonging the presence of OV agents and, consequently, their access to tumor cells [ 18 ]. Perhaps the most novel approach has been the coupling of CAR-T cells with OVs to help protect OVs from being cleared too quickly from the body [ 93 , 96 ].…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

“…JX-594 (Pexa-Vec) is a GM-CSF-enhanced vaccinia virus with a TK locus disruption to increase tumor selectivity [ 18 ]. Phase I and II trials for JX-594 have been completed in colorectal cancer and HCC, respectively, showing an acceptable safety profile, and demonstrating JX-594 to be overall well tolerated [ 137 , 138 , 139 ].…”

Section: Clinical Trialsmentioning

confidence: 99%

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From Benchtop to Bedside: A Review of Oncolytic Virotherapy

et al. 2016

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Oncolytic viruses (OVs) demonstrate the ability to replicate selectively in cancer cells, resulting in antitumor effects by a variety of mechanisms, including direct cell lysis and indirect cell death through immune-mediate host responses. Although the mechanisms of action of OVs are still not fully understood, major advances have been made in our understanding of how OVs function and interact with the host immune system, resulting in the recent FDA approval of the first OV for cancer therapy in the USA. This review provides an overview of the history of OVs, their selectivity for cancer cells, and their multifaceted mechanism of antitumor action, as well as strategies employed to augment selectivity and efficacy of OVs. OVs in combination with standard cancer therapies are also discussed, as well as a review of ongoing human clinical trials.

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Replication efficiency of oncolytic vaccinia virus in cell cultures prognosticates the virulence and antitumor efficacy in mice

Chen

Zhang

et al. 2011

J Transl Med

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BackgroundWe have shown that insertion of the three vaccinia virus (VACV) promoter-driven foreign gene expression cassettes encoding Renilla luciferase-Aequorea GFP fusion protein, β-galactosidase, and β-glucuronidase into the F14.5L, J2R, and A56R loci of the VACV LIVP genome, respectively, results in a highly attenuated mutant strain GLV-1h68. This strain shows tumor-specific replication and is capable of eradicating tumors with little or no virulence in mice. This study aimed to distinguish the contribution of added VACV promoter-driven transcriptional units as inserts from the effects of insertional inactivation of three viral genes, and to determine the correlation between replication efficiency of oncolytic vaccinia virus in cell cultures and the virulence and antitumor efficacy in miceMethodsA series of recombinant VACV strains was generated by replacing one, two, or all three of the expression cassettes in GLV-1h68 with short non-coding DNA sequences. The replication efficiency and tumor cell killing capacity of these newly generated VACV strains were compared with those of the parent virus GLV-1h68 in cell cultures. The virus replication efficiency in tumors and antitumor efficacy as well as the virulence were evaluated in nu/nu (nude) mice bearing human breast tumor xenografts.Resultswe found that virus replication efficiency increased with removal of each of the expression cassettes. The increase in virus replication efficiency was proportionate to the strength of removed VACV promoters linked to foreign genes. The replication efficiency of the new VACV strains paralleled their cytotoxicity in cell cultures. The increased replication efficiency in tumor xenografts resulted in enhanced antitumor efficacy in nude mice. Similarly, the enhanced virus replication efficiency was indicative of increased virulence in nude mice.ConclusionsThese data demonstrated that insertion of VACV promoter-driven transcriptional units into the viral genome for the purpose of insertional mutagenesis did modulate the efficiency of virus replication together with antitumor efficacy as well as virulence. Replication efficiency of oncolytic VACV in cell cultures can predict the virulence and therapeutic efficacy in nude mice. These findings may be essential for rational design of safe and potent VACV strains for vaccination and virotherapy of cancer in humans and animals.

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Oncolytic Virotherapy of Cancer

Cited by 7 publications

References 210 publications

Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer Agent

Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer Agent

From Benchtop to Bedside: A Review of Oncolytic Virotherapy

Replication efficiency of oncolytic vaccinia virus in cell cultures prognosticates the virulence and antitumor efficacy in mice

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