Treatment of spontaneously arising retinoblastoma tumors in transgenic mice with an attenuated herpes simplex virus mutant

C R Brandt; P D Imesch; N L Robinson; N A Syed; S Untawale; S R Darjatmoko; R J Chappell; P Heinzelman; D M Albert

doi:10.1006/viro.1996.8414

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Treatment of spontaneously arising retinoblastoma tumors in transgenic mice with an attenuated herpes simplex virus mutant

Journal article

Open access

Peer reviewed

Treatment of spontaneously arising retinoblastoma tumors in transgenic mice with an attenuated herpes simplex virus mutant

C R Brandt, P D Imesch, N L Robinson, N A Syed, S Untawale, S R Darjatmoko, R J Chappell, P Heinzelman and D M Albert

Virology (New York, N.Y.), Vol.229(1), pp.283-291

03/03/1997

DOI: 10.1006/viro.1996.8414

PMID: 9123872

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Abstract

The use of viruses to treat tumors has received renewed interest with the availability of genetically defined attenuated mutants. Herpes simplex virus (HSV) type 1 in particular has been shown to be effective for tumors of neuronal origin. However, the model systems used for these studies rely on the use of explanted tumor cells in immunodeficient animals. We have used a recently developed transgenic mouse model, wherein mice spontaneously develop retinoblastomas, to determine if a mutant HSV has a therapeutic effect against an endogenously arising tumor in an immunocompetent host. The injection of 1 x 10(6) PFU of the neuroattenuated HSV-1/HSV-2 recombinant RE6 into the vitreous of transgenic mice resulted in a significant inhibition of tumor growth compared to injection of medium alone (P = 0.0063). Immunohistochemical analysis of viral antigen showed that viral replication was restricted to focal areas of the tumors and the retinal pigment epithelium. Viral growth was not significantly different in the eyes of transgene-positive and transgene-negative mice, suggesting that enhanced replication in tumor cells may not explain the effects. Tumor cells in the treated eyes were significantly less differentiated than those in the untreated eyes (P = 0.04), suggesting that the virus may replicate better in certain cell types in the tumors. Although the injection of RE6 resulted in a difference in tumor size, the treatment did not result in the elimination of tumors in any of the mice improvements in the efficacy of tumor control are needed if this therapy is to be of use.

Eye Neoplasms - virology

Retinoblastoma - virology

Retinoblastoma - therapy

Mice, Inbred C57BL

Eye Neoplasms - pathology

Male

Mice, Transgenic

Eye Neoplasms - therapy

Retinoblastoma - pathology

Herpesvirus 1, Human - physiology

Animals

Mutagenesis

Virus Replication

Female

Herpesvirus 1, Human - genetics

Mice

Mice, Inbred BALB C

Details

Title: Subtitle: Treatment of spontaneously arising retinoblastoma tumors in transgenic mice with an attenuated herpes simplex virus mutant
Creators: C R Brandt - Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison 53706, USA
P D Imesch
N L Robinson
N A Syed
S Untawale
S R Darjatmoko
R J Chappell
P Heinzelman
D M Albert
Resource Type: Journal article
Publication Details: Virology (New York, N.Y.), Vol.229(1), pp.283-291
DOI: 10.1006/viro.1996.8414
PMID: 9123872
NLM abbreviation: Virology
ISSN: 0042-6822
eISSN: 1096-0341
Publisher: United States
Grant note: EY07736 / NEI NIH HHS EY01917 / NEI NIH HHS
Language: English
Date published: 03/03/1997
Academic Unit: Pathology; Ophthalmology and Visual Sciences
Record Identifier: 9983980005002771

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