Synergistic Activity of Anti-GD2 Antibody and CD47-Blockade for Immunotherapy of Neuroblastoma and Osteosarcoma
Lay Summary: Patients with relapsed neuroblastoma and osteosarcoma have limited therapeutic options and frequently die of their disease. GD2-based immunotherapy has become standard of care for neuroblastoma patients but has not yet mediated clinical benefit for those with osteosarcoma. Additionally, a large percentage of neuroblastoma patients who receive anti-GD2 immunotherapy eventually relapse. Therefore, there is a need to improve immunotherapy to benefit more patients. We have found that combining anti-GD2 therapy with an antibody that blocks CD47, a 'Don't Eat Me Signal' expressed by cancer, unleashes immune cells to phagocytose (eat) tumor cells.
Project Goal: We are currently translating this combination to clinical trials in children. This project focuses on understanding the biologic basis for this enhanced efficacy so that we can find future combination therapies to further extend the reach of immunotherapy in pediatric solid tumors.
Project Update 2024: We have translated this combination to clinical trials in children. This project focused on understanding mechanisms of efficacy and resistance to generate new therapeutic approaches that can reach more children with incurable cancers. Through this work, we have identified a new mechanism of resistance (GD2 loss) and have found ways to re-establish the efficacy of anti-GD2 antibodies that may be clinically relevant.
