Frameshift neoantigen (FS neoantigen)

Frameshift neoantigens are novel, tumor-specific peptides generated by frameshift mutations—insertions or deletions (indels) that shift the translational reading frame of mRNA (Turajlic et al., 2017, Lancet Oncology). These mutations result in entirely new amino acid sequences that are not present in the normal human proteome, making them highly immunogenic and less likely to be subject to central immune tolerance (Mandal et al., 2019, Nature). They are particularly prevalent in cancers with high microsatellite instability (MSI-H) or DNA mismatch repair deficiency (dMMR), such as Lynch syndrome-associated colorectal and endometrial cancers (Roudko et al., 2020, Science Translational Medicine). Therapeutic approaches, such as the NOUS-209 vaccine, target these neoantigens to induce potent CD8+ and CD4+ T-cell responses specifically against tumor cells (D'Alise et al., 2022, Science Translational Medicine). Because these antigens are absent in healthy tissue, they represent ideal targets for precision immunotherapy with a reduced risk of off-target toxicity (Gubin et al., 2015, Journal of Clinical Investigation).

Other names

Frameshift-derived peptideFrameshift mutation-derived neoantigenFSPFrameshift-derived neoantigen

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