CD47-blocking Oncolytic Vaccinia Viruses as Biotherapeutics for Pediatric Solid Tumors
The long-term goal of our research is to develop an effective therapy for children with solid tumors based on oncolytic vaccinia viruses (VVs). Oncolytic VVs are viruses that preferentially infect and kill cancer cells. While initial clinical studies have demonstrated their safety and clinical benefits in patients, no patient with large tumors has been cured. This is most like due to the inability of VVs to infect all tumor cells and activate the immune system. To overcome this limitation, we have designed a novel VV that secretes a molecule that blocks the so called 'don't eat me receptor' on cancer cells, sensitizing cancer cells to be killed by a type of immune cell called macrophage. Macrophages will also kill cancer cells that are not infected by VV, since our molecule is secreted.
In this particular application we now propose to optimize the antitumor activity of our VV for osteosarcoma, the most prevalent bone tumor in children. We will conduct studies in preclinical models that closely mimic human disease. At the end of the proposal we expect to have selected the optimal VV for further preclinical clinical development with the ultimate goal of conducting a clinical study in pediatric osteosarcoma patients.