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The Oncolytic Virus VSV-GP Is Effective against Malignant Melanoma

Previously, we described VSV-GP, a modified version of the vesicular stomatitis virus, as a non-neurotoxic oncolytic virus that is effective for the treatment of malignant glioblastoma and ovarian cancer. Here, we evaluate the therapeutic efficacy of VSV-GP for malignant melanoma. All of the human,...

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Autores principales: Kimpel, Janine, Urbiola, Carles, Koske, Iris, Tober, Reinhard, Banki, Zoltan, Wollmann, Guido, von Laer, Dorothee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869501/
https://www.ncbi.nlm.nih.gov/pubmed/29498639
http://dx.doi.org/10.3390/v10030108
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author Kimpel, Janine
Urbiola, Carles
Koske, Iris
Tober, Reinhard
Banki, Zoltan
Wollmann, Guido
von Laer, Dorothee
author_facet Kimpel, Janine
Urbiola, Carles
Koske, Iris
Tober, Reinhard
Banki, Zoltan
Wollmann, Guido
von Laer, Dorothee
author_sort Kimpel, Janine
collection PubMed
description Previously, we described VSV-GP, a modified version of the vesicular stomatitis virus, as a non-neurotoxic oncolytic virus that is effective for the treatment of malignant glioblastoma and ovarian cancer. Here, we evaluate the therapeutic efficacy of VSV-GP for malignant melanoma. All of the human, mouse, and canine melanoma cell lines that were tested, alongside most primary human melanoma cultures, were infected by VSV-GP and efficiently killed. Additionally, we found that VSV-GP prolonged the survival of mice in both a xenograft and a syngeneic mouse model. However, only a few mice survived with long-term tumor remission. When we analyzed the factors that might limit VSV-GP’s efficacy, we found that vector-neutralizing antibodies did not play a role in this context, as even after eight subsequent immunizations and an observation time of 42 weeks, no vector-neutralizing antibodies were induced in VSV-GP immunized mice. In contrast, the type I IFN response might have contributed to the reduced efficacy of the therapy, as both of the cell lines that were used for the mouse models were able to mount a protective IFN response. Nevertheless, early treatment with VSV-GP also reduced the number and size of lung metastases in a syngeneic B16 mouse model. In summary, VSV-GP is a potent candidate for the treatment of malignant melanoma; however, factors limiting the efficacy of the virus need to be further explored.
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spelling pubmed-58695012018-03-28 The Oncolytic Virus VSV-GP Is Effective against Malignant Melanoma Kimpel, Janine Urbiola, Carles Koske, Iris Tober, Reinhard Banki, Zoltan Wollmann, Guido von Laer, Dorothee Viruses Article Previously, we described VSV-GP, a modified version of the vesicular stomatitis virus, as a non-neurotoxic oncolytic virus that is effective for the treatment of malignant glioblastoma and ovarian cancer. Here, we evaluate the therapeutic efficacy of VSV-GP for malignant melanoma. All of the human, mouse, and canine melanoma cell lines that were tested, alongside most primary human melanoma cultures, were infected by VSV-GP and efficiently killed. Additionally, we found that VSV-GP prolonged the survival of mice in both a xenograft and a syngeneic mouse model. However, only a few mice survived with long-term tumor remission. When we analyzed the factors that might limit VSV-GP’s efficacy, we found that vector-neutralizing antibodies did not play a role in this context, as even after eight subsequent immunizations and an observation time of 42 weeks, no vector-neutralizing antibodies were induced in VSV-GP immunized mice. In contrast, the type I IFN response might have contributed to the reduced efficacy of the therapy, as both of the cell lines that were used for the mouse models were able to mount a protective IFN response. Nevertheless, early treatment with VSV-GP also reduced the number and size of lung metastases in a syngeneic B16 mouse model. In summary, VSV-GP is a potent candidate for the treatment of malignant melanoma; however, factors limiting the efficacy of the virus need to be further explored. MDPI 2018-03-02 /pmc/articles/PMC5869501/ /pubmed/29498639 http://dx.doi.org/10.3390/v10030108 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kimpel, Janine
Urbiola, Carles
Koske, Iris
Tober, Reinhard
Banki, Zoltan
Wollmann, Guido
von Laer, Dorothee
The Oncolytic Virus VSV-GP Is Effective against Malignant Melanoma
title The Oncolytic Virus VSV-GP Is Effective against Malignant Melanoma
title_full The Oncolytic Virus VSV-GP Is Effective against Malignant Melanoma
title_fullStr The Oncolytic Virus VSV-GP Is Effective against Malignant Melanoma
title_full_unstemmed The Oncolytic Virus VSV-GP Is Effective against Malignant Melanoma
title_short The Oncolytic Virus VSV-GP Is Effective against Malignant Melanoma
title_sort oncolytic virus vsv-gp is effective against malignant melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869501/
https://www.ncbi.nlm.nih.gov/pubmed/29498639
http://dx.doi.org/10.3390/v10030108
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