Evaluation of ganciclovir-mediated enhancement of the antitumoral effect in oncolytic, multimutated herpes simplex virus type 1 (g207) therapy of brain tumors

ABSTRACT G207 is a multimutated, conditionally replicating herpes simplex virus type 1 (HSV-1) that retains an intact viral thymidine kinase (HSV-tk) gene. The virus exhibits oncolytic

activity in various tumors and is being evaluated in patients with recurrent malignant glioma. In view of the potential for ganciclovir (GCV) to either enhance or inhibit the antitumoral

activity of HSV-tk-retaining HSV-1 vectors, we evaluated the effect of GCV administration on the antitumoral activity of G207. In culture, addition of GCV either had no effect or inhibited

the cytocidal action of G207 at replication-permissive temperatures, while it significantly increased the cell killing in three of the four cell lines studied when virus replication was

inhibited at nonpermissive temperatures. Using a G207-permissive immunocompetent mouse tumor model, subcutaneous N18 neuroblastoma in syngeneic A/J mice, we found that GCV treatment did not

affect G207-mediated tumor growth inhibition at a variety of viral doses (105, 107, and 107 × 2 plaque-forming units). In A/J mice harboring intracerebral N18 tumors, GCV administration had

no significant effect on the prolongation of survival by G207 inoculation. These findings suggest that GCV administration may not be beneficial to the efficacy of G207 tumor therapy under

conditions that favor active viral replication, because the potential HSV-tk/GCV-mediated enhancement of G207 oncolytic activity may be balanced out by the inhibitory action of GCV on viral

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EXPRESSING IMMUNOMODULATORY TRANSGENE THERAPY FOR MALIGNANT GLIOMAS Article Open access 25 June 2020 AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Neurosurgery, Molecular

Neurosurgery Laboratory, Georgetown University Medical Center Washington, 20007, District of Columbia Tomoki Todo, Samuel D Rabkin & Robert L Martuza * Department of Microbiology and

Immunology, Georgetown University Medical Center Washington, 20007, District of Columbia Samuel D Rabkin Authors * Tomoki Todo View author publications You can also search for this author

inPubMed Google Scholar * Samuel D Rabkin View author publications You can also search for this author inPubMed Google Scholar * Robert L Martuza View author publications You can also search

for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Todo, T., Rabkin, S. & Martuza, R. Evaluation of

ganciclovir-mediated enhancement of the antitumoral effect in oncolytic, multimutated herpes simplex virus type 1 (G207) therapy of brain tumors. _Cancer Gene Ther_ 7, 939–946 (2000).

https://doi.org/10.1038/sj.cgt.7700182 Download citation * Received: 08 September 1999 * Accepted: 27 December 1999 * Published: 15 June 2000 * Issue Date: 01 June 2000 * DOI:

https://doi.org/10.1038/sj.cgt.7700182 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not

currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * Herpes simplex virus * viral therapy * ganciclovir *

bystander effect * thymidine kinase * brain neoplasm.