Analysis of Fusion Genes in Ewing Sarcoma for Immuno-Oncology
The proposed research will use new information to make mRNA vaccines against products of a cancer specific gene, EWS, involved in Ewing sarcoma and desmoplastic small round cell tumor (DSRCT). These rare cancers in young people always are associated with the broken apart EWS gene that is fused to another gene such as FLI1, ERG, or WT1. Analysis of EWS cancer-specific sequences has shown >70% of Ewing sarcoma tumors and DSRCT metastases have the EWS gene break and fusion to FLI1 or WT1 at the exactly same place in the genome EWS exon 7. This new information makes it possible to design a clinical trial against EWS-FLI 1 and EWS-WT1 expression in cancer cells in a manner similar to generating immunity against a viral infection. What is novel is that the proposed research is dual mRNA and immune booster approach to generate more rapid, higher, and longer lasting immune responses which are necessary for both cancer cell destruction and relapse prevention.