Viruses · 2018
The Oncolytic Virus VSV-GP Is Effective against Malignant Melanoma.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Kimpel Janine, Urbiola Carles, Koske Iris, Tober Reinhard, Banki Zoltan, Wollmann Guido, von Laer Dorothee
Аннотация
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.
Предметные рубрики MeSH
AnimalsAntibodies, NeutralizingCell Line, TumorCytopathogenic Effect, ViralDisease Models, AnimalDogsHumansInterferon Type IMelanomaMelanoma, ExperimentalMiceNeoplasm MetastasisOncolytic VirotherapyOncolytic VirusesTumor BurdenVesicular stomatitis Indiana virusViral TropismVirus ReplicationXenograft Model Antitumor Assays