Grant: Project Grant

Osteosarcoma (OS) is the most common primary malignant bone tumor and the fifth most common primary malignancy among adolescents and young adults. Unfortunately, overall survival is approximately 70%, with no meaningful improvement realized in over 20 years. Patients with metastatic disease to the lungs and to the bone generally have poor outcomes, with an overall survival of less than 40% and 20%, respectively. In addition, OS demonstrates sweeping genetic variability from one tumor to the next which makes it challenging to pursue conventional targeting approaches. In our previous studies we have found out that a protein called Insulin Growth Factor Receptor Type 2 (IGF2R) is consistently expressed on all OS cell lines, including the ones derived from patients. When targeting the experimental OS tumors in mice with the mouse antibodies to the IGF2R protein, which were carrying the radioactive "payload" capable of destroying tumor cells, we observed considerable slowing down of tumor growth without side effects. However, to move this encouraging approach into the clinical trials, we need two things: make human antibodies to IGF2R which would allow to treat patients multiple times without side effects from the immune system, and to test these antibodies in the animals with the tumors comparable to human ones. It turns to be that OS is one of the most widespread cancers in companion dogs, it very closely resembles human OS, and treatments for dogs are very limited. Thus, our hypothesis is that we will be able to create highly IGF2R-specific human antibodies which would effectively target OS tumor cells in companion dogs with OS and deliver curative tumoricidal doses of radioactivity to the tumors without toxicity to normal organs. If successful, this project will generate the antibodies and the data needed to move this approach into the clinical trials in patients with OS, and, as added benefit, will create the treatment for companion dogs with OS.