SBIR FY25 CONCEPT AWARD, DEVELOPMENT OF AN IMMUNOTHERAPY FOR EWING SARCOMA USING A NOVEL MURINE MODEL

Ewing sarcoma (ES) is rare pediatric cancer that afflicts ~500 patients each year in the US and the standard of care for ES still revolves around the same chemotherapy and radiation regimes that have been used since the 1980s. The lack of effective therapies is apparent in the 25% 5-year survival rate for ES patients with metastatic or recurrent disease. Our group has discovered that the protein USP6 upregulates multiple, distinct immunostimulatory pathways. Delivery MER-101 (encoding the USP6 protein) recapitulates the immunostimulatory effects of USP6 in ES. Despite decades of research, there are no immune-competent mouse models of ES, which limits the field to xenotransplanting human ES into mice lacking adaptive immunity. The lack of an immune-competent ES mouse model limits the translational applicability of pre-clinical ES immunotherapies. However, mice that are reconstituted with a fully mature human immune system offer an attractive immune-competent alternative model. We are seeking to evaluate MER-101 in humanized mice and to simultaneously characterize ES biology in a fully immune-competent system. Successful completion of these studies will support a Phase II SBIR as well as IND-enabling studies utilizing a mouse model that better recapitulates ES biology and the human disease.