Design of modified measles virus for cancer treatment – OncoMeVax

Our consortium has developed a new cancer treatment based on virotherapy using a modified form of measles vaccine virus. Oncovirotherapy has recently emerged as a credible alternative to conventional anticancer therapies. It consists in treating tumors with a virus able to specifically kill tumor cells while preserving healthy cells. Data from the literature and our work have shown that attenuated measles vaccine virus (MV) is an extremely powerful oncolytic virus for the treatment of many cancers. Several human trials using MV have shown clinical benefits for the treatment of cutaneous T cell lymphoma, ovarian cancer and disseminated multiple myeloma.

During the last years we conducted a series of studies showing that the Schwarz MV vaccine strain can infect and kill several types of cancer cells: malignant pleural mesothelioma, melanoma, colon and lung adenocarcinomas. We demonstrated that 75% of patients might be sensitive to this treatment. We also showed that MV infection of tumor cells induces immunogenic death and activates antitumor immune response by breaking tumor tolerance, thus potentially preventing relapse and metastasis.

Recently, we generated a modified MV that specifically induces a faster and stronger apoptosis of infected tumor cells, allowing a therapeutic activity before recall of pre-existing immunity to measles that might prevent action. This MVDeltaC virus was modified by inactivation of a virulence factor (the viral protein C), which usually facilitates virus spreading by delaying apoptosis of infected cells. Our studies support the initiation of clinical trials to test the efficacy of MVDeltaC against several cancers. The start-up company OncoVITA was created at Institut Pasteur based on a large patent portfolio to ensure the Good Manufacturing Process (GMP), the clinical development, and the commercial exploitation of this new oncolytic treatment.

The present program has two objectives. The first is to extend fundamental research to understand the mechanism of action of MVDeltaC, particularly by identifying in cancer cells the pro and anti-apoptotic host factors that are controlled by the C protein of measles virus. This research will provide biomarkers allowing selecting patients sensitive to MVDeltaC treatment. The second objective is to perform the regulatory preclinical studies that are required before clinical trials with MVDeltaC. The proposed studies consist in i) developing a new mouse model to validate the role of immunity in treatment, ii) developing the GMP production process of MVDeltaC, iii) extending the analysis to other tumor cells, iv) testing the treatment efficacy in vitro in the presence of chemotherapy agents, v) evaluating the effect of anti-measles antibodies.

We believe that this new generation of cancer treatment based on a mostly safe and reassuring common vaccine will participate to the actual renewal of oncology treatments. Through collaboration between Institut Pasteur, Inserm and OncoVITA, this program will allow transferring an innovative technology from research to clinical development.