Evaluating Treatment Of Mouse Tumors With Natural Oncolytic Viruses

Oncolytic viruses infect and kill cancer cells while leaving normal cells intact and may act on the tumor as well as metastases. The main obstacle of virotherapy is neutralization of the treatment by the patient own immune system. The ability to switch and use a new strain of virus for treatment after the rise of an immunological response, enable to overcome this major obstacle and allow prolonged treatment. Such a treatment will overcome an immune response against the virus and prevent escape of the tumor thus, enabling treatment of a range of cancers originated from various mutations. In this study we developed a method of screening for oncolytic potential of veterinary viruses. The source of the virus may be avian or mammalian source thus decreasing the potential danger to humans. The ability of those viruses to kill murine tumor cells was evaluated in vitro. There was no apparent correlation between the virus virulence and its capability to destruct malignant cells. We characterized all candidate viruses by TCID₅₀ /ml assay in VERO cell line. Then, we performed MTT tests on 6 different murine cancer cell lines to determine the activity of the viruses. There were differences in the effect of viruses on the various cell lines. Based on the results of the tests we focused on 3 distinct viruses for in vivo tests in mice. The study evaluated the potential of sequentially administered oncolytic veterinary viruses, which we have characterized, to treat cancer in an immunocompetent murine model. The variety of potential oncolytic viruses in arsenal and the possibility to use combinations of viruses (as cocktail or one by one) may allow repeated treatments, overcoming the immune response on one hand and attacking the tumor by more than one mechanism on the other hand.