Grant: CIHR Fellowship

Triple-negative breast cancer is the most deadly form of breast cancer. There is a need to develop new treatment alternatives for patients with recurring disease or resistant cancers. By combining novel therapies, we expect to develop an effective treatment strategy. The treatment of cancer with oncolytic viruses (OV), which specifically target tumor cells while leaving normal tissues intact, is a field that is rapidly progressing. There are currently many promising clinical trials around the world that use this strategy. While breast cancer shuts down the anti-tumor immune response, OVs were shown to induce anti-tumor immunity. We modified an OV to be a more potent immune stimulator by expressing interferon gamma (IFNg), a powerful immune-stimulant. The idea is that it will stimulate the immune system to generate a specific immune response against the tumor. Although the IFNg virus is efficient in our hands, we could not cure tumor-bearing mice. Our aim is to optimize the treatment and achieve cures. We found that, in response to the virus, tumors augment their expression of the immune-suppressive molecule PDL1. Our hypothesis is that the combination of our OV with a PDL1-blocking antibody will synergize and offer a better treatment. Another strategy is to increase the replication of the virus. The treatment of various cell lines with the drug Paclitaxel led to an increase in virus production. We will investigate if its combination with our OV and the PDL1 antibody is sufficient to cure the animals. To determine the precise effects of the treatments in the mouse model, we will monitor the virus in the primary tumor and metastasis, as well as its ability to activate an immune response against the tumor. The presence and activation state of different immune cells in the tumor and immune organs will therefore be assessed. Finally, tumor progression and metastasis, as well as survival, will be evaluated in mice treated with our combination of OV, drug and antibody.