RNA-nanoparticle (RNA-NP) vaccine for ARMS
Project Goal: In this project, we aim to target the PAX3-FOXO1 fusion in a reliable ARMS murine model to support a pre-manufactured vaccine that doesn’t require personalization. We will also study the mechanisms behind immune escape that could lead to improving drug de
Institution: University of Florida Pediatric Cancer Immunotherapy Initiative
Researchers: Leighton Elliott, MD
Year Awarded: 2023
Type of Childhood Cancer: Rhabdomyosarcoma (RMS)
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. Alveolar rhabdomyosarcoma (ARMS) predicts worse outcomes and is most commonly driven by PAX3-FOXO1 or PAX7-FOXO1 gene fusions. Immunotherapy may provide long-term immunity with minimal adverse effects. RMS lacks response to immune checkpoint inhibition. Recently, personalized mRNA cancer vaccines have demonstrated expanded immune response and prolonged survival in early phase clinical trials in pancreatic cancer and melanoma. Dendritic cell vaccine successes in RMS also support the notion to further develop novel cancer vaccines. Our RNA-nanoparticle (RNA-NP) vaccine is unique due to its multilamellar structure allowing for more mRNA loading and a robust innate immune response. Preclinically, we have successfully treated murine and/or canine models with osteosarcoma, melanoma, and high-grade gliomas. Our vaccine can use total tumor RNA (ttRNA) or target-specific RNA to provide a significant survival advantage. In this project, we aim to target the PAX3-FOXO1 fusion in a reliable ARMS murine model to support a pre-manufactured vaccine that doesn’t require personalization. We will also study the mechanisms behind immune escape that could lead to improving drug development. Since our vaccine is currently being studied in clinical trial, the success of this project will lead directly into subsequent clinical trials for RMS and other fusion-driven sarcomas.