Ewing sarcoma breakpoint region 1-ETS transcription factor ERG fusion protein-derived peptide antigen (EWS-ERG peptide antigen)

EWS-ERG fusion protein-derived peptide antigens are tumor-specific neoantigens resulting from the t(21;22)(q22;q12) chromosomal translocation, which occurs in approximately 5-10% of Ewing sarcoma cases (Sorensen et al., 1994, Nature Genetics). This translocation fuses the EWSR1 gene with the ERG gene, creating a chimeric protein that acts as an aberrant transcription factor driving oncogenesis (UniProt Q01844, P11308). The unique amino acid sequence at the fusion junction is not found in the normal human proteome, making it a highly specific target for immunotherapy (Evans et al., 2012, Clinical Cancer Research). These junctional peptides can be processed and presented by Major Histocompatibility Complex (MHC) molecules, particularly HLA-A*02:01, on the surface of tumor cells (Dozier et al., 2003, Journal of Immunology). Therapeutic strategies targeting these antigens include peptide-based vaccines and T-cell receptor (TCR) engineered T-cell therapies designed to induce a cytotoxic T-lymphocyte response (CTL) against the tumor. While promising, the efficacy of these treatments can be limited by the low expression of MHC molecules on Ewing sarcoma cells and the immunosuppressive nature of the tumor microenvironment.

Other names

EWSR1-ERG fusion peptideEWS-ERG neoantigenEWS-ERG junctional peptidet(21;22) fusion peptide

Induction of a targeted T-cell mediated immune response against tumor cells presenting the fusion-specific neoepitope via MHC Class I molecules.