Patient-specific frameshift-derived neoantigen (FSN)

Patient-specific frameshift-derived neoantigens are novel peptides generated by frameshift mutations, such as insertions or deletions (indels) that alter the open reading frame of a gene (Turajlic et al., 2017, Lancet Oncology). Unlike single nucleotide variants, frameshift mutations result in entirely new, long C-terminal amino acid sequences that are completely foreign to the host's immune system, making them highly immunogenic (Smith et al., 2019, Science). These neoantigens are particularly abundant in tumors with microsatellite instability (MSI) or mismatch repair deficiencies (Le et al., 2015, NEJM). In therapeutic contexts, these antigens are identified through genomic sequencing and used to develop personalized cancer vaccines, such as mRNA-4157, or TCR-engineered T-cell therapies (Sahin et al., 2017, Nature). By training the immune system to recognize these unique non-self signatures, these treatments aim to induce a robust and specific anti-tumor T-cell response. This approach minimizes the risk of central tolerance and off-target effects on healthy tissues, as the sequences are not present in the normal human proteome (Roudko et al., 2020, Science Translational Medicine).

Other names

Frameshift neoantigenFrameshift-derived peptideIndel-derived neoantigenFSPFrameshift-derived antigen

Induction of a patient-specific T-cell mediated immune response against tumor cells by presenting novel, non-self peptide sequences on Major Histocompatibility Complex (MHC) molecules.