A Novel Approach Combining Oncolytic Virotherapy and Dual Immune Checkpoint Blockade for Metastatic Osteosarcoma
Abstract
FY19 PRCRP Topic Areas and Military Health Focus Area: This project will address three FY19 PRCRP Topic Areas: (1) Cancer in Children, Adolescents, and Young Adults (AYAs); (2) Immunotherapy, and (3) Rare Cancers and the Military Health Focus Area of “Gaps in cancer prevention, early detection/diagnosis, prognosis, treatment, and/or survivorship that affect the general population but have a particularly profound impact on the health and well-being of military Service members, Veterans, and their beneficiaries.” Scientific Objective and Rationale: Our objective is to test the safety and efficacy of an innovative treatment for bone cancer that has metastasized, or spread, to the lungs. The treatment consists of an engineered virus that infects and kills tumor cells, exposing them to the immune system, combined with a small protein that disables the immune-inhibitory effects of the tumor. We will use well-established laboratory animal models of metastatic bone cancer to identify an optimal dose, as well as an appropriate frequency of administration for each component of the treatment. These models will also enable us to determine how the combination therapy works. Next, we will test this combination in pet dogs with spontaneous metastatic bone cancer. This approach has a dual, simultaneous benefit to help us evaluate the treatment in a clinically realistic setting, so we can learn how it could be applied to children and AYAs with metastatic bone cancer, and to help dog “patients,” potentially including service dogs, with metastatic bone cancer that otherwise face inevitable death from their disease. This “path to translation” from laboratory models to pet dogs with naturally occurring disease can inform the design of clinical trials and accelerate implementation of the therapy for human cancer patients. Near Term Impact and Applicability of the Research: The use of drugs that activate the immune system to kill cancer, so called “immunotherapy,” has transformed the care and outcomes for many adult cancer patients. But the promise of immunotherapy has not been realized for children, and specifically for bone cancer patients. Our approach combines three steps to enhance the success of immunotherapy, specifically with the intent to help children and AYAs with an incurable, highly metastatic type of cancer. In the near term (3-5 years), our study will create knowledge to inform how to use this novel treatment in children and AYAs with bone cancer. It will allow us to establish guidelines for how to dose the drugs, and at what frequency, in early stage clinical trials. It will also allow us to develop estimates for efficacy and to anticipate possible toxicity. In the medium term (5-8 years), our work will provide a foundation to understand which patients would actually benefit from this treatment. In the long term (5-20 years), this therapy could find applications against other metastatic tumors. How is the proposed research relevant to active duty Service members, Veterans, and other military beneficiaries? About 32 of every 100,000 children under 14 years are diagnosed with cancer every year in the US. While relatively rare, the American Cancer Society still lists cancer as the leading cause of disease-induced death past infancy and second overall as a cause of death for children. Cancer is more common in 15 to 39 year-old AYAs: there are about 139 diagnoses per 100,000 individuals in the US, making cancer the #1 disease killer in this age group. Children and AYAs comprise more than half of the American public; yet, the National Cancer Institute states that cancers in these populations are under-studied, leading to much suffering and death. We will address the Military Health Focus Area of “Gaps in cancer prevention, early detection/diagnosis, prognosis, treatment, and/or survivorship that affect the general population but have a particularly profound impact on the health and well-being of military Service members, Veterans,
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010682
Entities
People
- Jaime Modiano
Organizations
- United States Army
- University of Minnesota