Frameshift-derived neopeptides (FSP)

Frameshift-derived neopeptides are novel amino acid sequences produced when insertions or deletions (indels) in DNA alter the reading frame of a gene during translation (Turajlic et al., Lancet Oncol, 2017). These sequences are entirely foreign to the host immune system, as they do not exist in the normal human proteome, which leads to high immunogenicity and a lower risk of central tolerance compared to single nucleotide variants (Mandal et al., Nature, 2019). They are most frequently observed in cancers with high microsatellite instability (MSI-H) or deficient DNA mismatch repair (dMMR), such as Lynch syndrome-associated colorectal and endometrial cancers (Ballhausen et al., Nat Commun, 2020). In therapeutic contexts, these neopeptides serve as potent targets for personalized cancer vaccines and TCR-engineered T-cell therapies designed to elicit a robust cytotoxic T-cell response against tumor cells (Nouscom, 2024). By targeting these unique antigens, clinicians aim to achieve high tumor specificity while minimizing off-target effects on healthy tissues.

Other names

Frameshift peptidesFS-neopeptidesFrameshift-derived neoantigensIndel-derived neoantigensFrameshift mutations-derived antigens

Induction of tumor-specific cytotoxic T-lymphocyte (CTL) responses by presenting novel, non-self peptide sequences on Major Histocompatibility Complex (MHC) molecules.