Ewing sarcoma breakpoint region 1-Friend leukemia virus integration 1 fusion protein-derived neoantigen peptide (EWS-FLI1 neoantigen peptide) (EWS-FLI1 neoantigen peptide)

Ewing sarcoma breakpoint region 1-Friend leukemia virus integration 1 (EWS-FLI1) fusion protein-derived neoantigen peptides are tumor-specific antigens arising from the pathognomonic t(11;22)(q24;q12) chromosomal translocation [1, 11]. This translocation fuses the N-terminal transactivation domain of EWSR1 with the C-terminal DNA-binding domain of FLI1, creating a unique amino acid sequence at the fusion junction that is absent in healthy tissues [1, 13]. These junctional sequences can be processed into short peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, most notably HLA-A*02:01 [1, 7]. As highly specific neoantigens, they serve as ideal targets for precision immunotherapies, such as T-cell receptor (TCR) engineered T-cell therapy and cancer vaccines, aimed at inducing a cytotoxic T-lymphocyte response against Ewing sarcoma cells [1, 10]. Despite their high specificity, therapeutic challenges include the low mutational burden of these tumors, potential HLA downregulation, and the immunosuppressive nature of the tumor microenvironment [2, 14]. Current research focuses on optimizing peptide binding affinity and TCR specificity to enhance the efficacy of adoptive cell transfers in patients with metastatic or recurrent disease [1, 7].

Other names

EWS-FLI1 junctional peptideEWSR1-FLI1 fusion neoantigenEWS-FLI1 breakpoint peptideEWS-FLI1 fusion-specific epitope

Recognition of the tumor-specific peptide-HLA complex by engineered T-cell receptors (TCRs) to induce cytotoxic T-lymphocyte-mediated lysis of cancer cells.