VSV-GP Technology

In recent years, several OVs have been developed and tested. Clinical trials have shown some therapeutic efficacy and much has been learnt on OV biology and modes of action. Meanwhile, there is a general agreement on the requirements of the "ideal" OV. However, none of the current OVs have so far met all these requirements.

The "ideal OV" should:

1. be highly specific for cancer cells;
2. kill cancer cells rapidly and effectively;
3. be non-pathogenic for the host and not integrate into the host genome;
4. allow arming with anti-cancer genes;
5. grow to high titers for production;
6. not be prevalent in the human population, so that the treated patients are not primarily immune to the OV (a problem of many OVs currently under development);
7. not readily induce a protective immune response (neutralizing antibodies) to the virus itself, which reduces the efficacy of repeated OV application - a problem of all OVs currently under development, besides ViraTherapeutics’ VSV-GP.

ViraTherapeutics' proprietary oncolytic virus VSV-GP fulfills all criteria of an ideal OV

• VSV-GP is effective against a broad range of cancers and is ViraTherapeutics' unique platform for a new class of innovative OV-based anti-cancer therapeutics.
• The highly specific lysis of malignant cells by VSV-GP is enabled by a defective anti-viral response of cancer cells.
• VSV-GP is extremely rapid and efficient in killing human cancer cells. VSV-GP's life cycle is shorter than for other OV platforms currently under development.
• VSV-GP has been modified to avoid neural inflammation associated with wild-type viruses. It is non-neurotoxic and safe in pre-clinical models.
• VSV-GP is not mutagenic, does not integrate into the host genome and, if necessary, can be armed with additional genes.
• VSV-GP grows rapidly to high titers in a broad range of different cell lines allowing efficient large scale production with standard technologies.
• Naturally, VSV infects rodents and livestock, whereas infections of humans are extremely rare and usually asymptomatic. Thus, there is no relevant preexisting immunity in the human population that could hinder the infection of tumor cells with VSV-GP and subsequent oncolysis.
• In VSV-GP the glycoprotein of the Vesicular Stomatitis Virus has been replaced by the glycoprotein of the Lymphocytic Choriomeningitis Virus (LCMV) to conceal the virus from the immune system. In preclinical models it did not induce virus neutralizing antibodies, potentially enabling repeated administration. This could allow ground-breaking applications of this novel treatment approach.

Scientific publications on VSV-GP

• Muik, A., Stubbert, L.J., Jahedi, R.Z., Geiß, Y., Dold, C., Tober, R., Volk, A., Klein, S., Dietrich, U., Yadollahi, U., Falls, T., Miletic, H., Stojdl, D., Bell, J.C. & von Laer, D. A highly potent chimeric oncolytic virus for the treatment of brain cancer. Cancer Res, 74(13):3567-78 (2014)
• Tober, R., Banki, Z., Egerer, L., Muik, A., Behmüller, S., Kreppel, F., Greczmiel, U., Oxenius, A., von Laer, D. & Kimpel, J. VSV-GP: a potent viral vaccine vector that boosts the immune response upon repeated applications. J Virol, 88(9):4897-907 (2014)
• Muik, A., Dold, C., Geiß, Y., Volk, A., Werbizki, M., Dietrich, U. & von Laer, D. Semireplication-competent vesicular stomatitis virus as a novel platform for oncolytic virotherapy. J Mol Med (Berl), 90(8):959-70 (2012)
• Muik, A., Kneiske, I., Werbizki, M., Wilflingseder, D., Giroglou, T., Ebert, O., Kraft, A., Dietrich, U., Zimmer, G., Momma, S. & von Laer, D. Pseudotyping vesicular stomatitis virus with lymphocytic choriomeningitis virus glycoproteins enhances infectivity for glioma cells and minimizes neurotropism. J Virol, 85(11):5679-84 (2011)