Imaging response to CD47 mAb immunotherapy in pediatric patients with osteosarcoma

Children with metastatic bone cancer have a poor prognosis, with an overall survival rate of less than 30%. Stanford investigators developed a new drug, monoclonal antibodies against the cancer cell marker CD47 (CD mAb), which activates specific immune cells (macrophages) in osteosarcomas to attack and eliminate cancer cells. Preclinical efficacy studies of CD47 mAb in animal models have been finalized and a phase I clinical trial will be initiated at Stanford in 2020. Since osteosarcomas will not decrease in size in response to CD47 mAb therapy, at least not in the immediate post-treatment phase, we need to develop new imaging tests to determine, who will respond to this new treatment. Our team recently developed a macrophage imaging test with iron oxide nanoparticles, which are phagocytosed by TAM and which can be detected with MRI. The goal of our study is to evaluate, if this new nanoparticle enhanced MR imaging test can non-invasively diagnose tumor response to CD47 mAb immunotherapy. To accomplish this goal, we will correlate ferumoxytol-tumor MRI enhancement with response to CD47 mAb therapy in pediatric osteosarcomas. We hypothesize that ferumoxytol-MRI will reveal increased enhancement of CD47 mAb treated tumors compared to untreated controls, and that the degree of nanoparticle enhancement will correlate with histological tumor response, as measured by the extent of tumor necrosis. Developing this imaging test could represent a significant breakthrough for clinicians as a new means for predicting tumor response to novel cancer immunotherapies. This pilot project will directly benefit an upcoming clinical trial at Stanford and provide preliminary data for future multi-center applications.