Mentor Name: Brian Ladle

Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults. While the use of multiagent chemotherapy significantly improves survival for these patients, unfortunately, treatment outcomes have not improved in decades. New approaches are desperately needed to improve the standard chemotherapy regimen of Methotrexate, doxorubicin (Adriamycin), and cisPlatin (MAP). Our lab has been investigating intratumoral (IT) delivery of ADU-S100, a stimulator of interferon genes (STING) agonist, in a groundbreaking canine OS clinical trial and in murine OS models. In our murine models, we have observed remarkable anti-tumor responses, including complete tumor regression, when ADU-S100 is given in combination with chemotherapy in about 40% of treated mice. We are investigating mechanisms that we can target to improve this response rate. The immunosuppressive signaling molecule TGF-beta is incredibly abundant in OS, and we hypothesize that blocking signaling from TGF-beta will improve the immune responses seen when mice are treated with our STING agonist + chemotherapy combination.