Tumor-specific neoantigen peptides and sarcoma fusion breakpoint peptides (TSNA/SFBP)

Tumor-specific neoantigen peptides (TSNAs) are novel amino acid sequences arising from somatic mutations, such as single nucleotide variants or indels, that are presented on the cell surface by Major Histocompatibility Complex (MHC) molecules (Schumacher & Schreiber, 2015 [1]). Sarcoma fusion breakpoint peptides are a distinct subset of neoantigens created by the junction of chromosomal translocations, which are pathognomonic for many sarcoma subtypes like Ewing sarcoma (EWS-FLI1) and synovial sarcoma (SS18-SSX) (Pollack et al., 2018 [2]). Because these sequences are entirely absent from the normal human proteome, they serve as ideal targets for immunotherapy, minimizing the risk of central tolerance and off-target autoimmune toxicity (Gryder et al., 2017 [3]). Therapeutic interventions targeting these peptides include personalized vaccines, such as mRNA-4157, and adoptive T-cell therapies designed to recognize the specific peptide-MHC complex (Weber et al., 2024 [4]; Yang et al., 2022 [5]). These targets are particularly valuable in 'cold' tumors like sarcomas, where the fusion-derived neoantigen may be the primary driver of the immune response (D'Angelo et al., 2018 [6]).

Other names

NeoantigensTumor-specific antigensFusion-derived neoantigensBreakpoint-spanning peptidesTSAsFusion-junction peptides

Induction of antigen-specific T-cell mediated cytotoxicity through the recognition of peptide-MHC complexes on tumor cells.