A Novel Approach Combining Oncolytic Virotherapy and Dual Immune Checkpoint Blockade for Metastatic Osteosarcoma
Abstract
Osteosarcoma is one of the most common cancers of children and adolescents and young adults (AYAs). The outcomes for with metastatic osteosarcoma are especially dismal because there are no effective options to treat this condition. Our objectives are to tilt the immune landscape of metastatic osteosarcoma from immunosuppression to immunoreactivity, and to generate preclinical support to translate this innovative immunotherapy for the treatment of children and AYAs with metastatic bone cancer. To achieve this, we propose to combine an oncolytic virus, which will kill tumor cells and activate the immune system in the tumor environment, with a drug that blocks the myeloid checkpoint to enhance phagocytosis and antigen presentation as well as the immune exhaustion checkpoint to enhance tumor killing by T cells and NK cells. We will define optimal combinations in lab animal models and subsequently use these data to translate the approach into a therapy for dogs with naturally occurring metastatic osteosarcoma, which will serve as a clinically realistic model in the pathway towards applying this therapy to treat children and AYAs with metastatic osteosarcoma.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1190887
Entities
People
- Jaime F. Modiano
- Shruthi Naik
Organizations
- Mayo Clinic
- University of Minnesota