Developing a Mouse Model of Metastatic Osteosarcoma for Immunotherapy

Abstract

Osteosarcoma is a primary bone malignancy that primarily affects children and young adults. The 5-year survival rate for patients with localized osteosarcoma is 60-70% and only 20% for patients who present metastasis at the diagnosis. The standard of care treatment has not improved the prognosis in over 30 years and new approaches addressing tumor resistance and immune evasion are required. The long-term goals of this project are to address two objectives: i) To study the potential benefits and risks of immunotherapeutic drugs eBAT and ONIx on syngeneic mouse models of metastatic osteosarcoma, and ii) To study their mechanism of action. K7M2 is a well-characterized model of spontaneous pulmonary metastasis, but intravenous injection of these cells did not result in lung colonization, at any dosage, in the mice in our study. We inferred from the data that the tumor cells were rejected by the immune-competent host. To study the mechanism of action of ONIx, we have made progress in optimizing the protocol for the phagocytosis assay, and further analysis with a different target cell line is planned. Assays to verify the mechanism of action of eBAT are being planned. Overall, this project provided significant learnings on objective planning and designing of the experiments and provided opportunities to acquire expertise in several new methodologies.