Frameshift peptide neoantigens (FSP neoantigens)

Frameshift peptide (FSP) neoantigens are novel, tumor-specific amino acid sequences resulting from insertion or deletion mutations within coding microsatellites (Ballhausen et al., 2020). These mutations are characteristic of tumors with deficient mismatch repair (dMMR) systems, leading to high microsatellite instability (MSI-H) (Mandal et al., 2019). Because these frameshifts shift the reading frame of the DNA, they produce entirely new peptide sequences that the immune system recognizes as foreign or non-self (Schwitalle et al., 2008). These FSPs are highly immunogenic and are often shared across different patients with MSI-H tumors, making them attractive targets for off-the-shelf cancer vaccines and T-cell therapies (D'Alise et al., 2020). By targeting these neoantigens, therapies aim to stimulate a robust T-cell response specifically against the cancer cells while sparing healthy tissue (Le et al., 2015).

Other names

Frameshift-derived neoantigensMSI-induced frameshift peptidesFrameshift peptidesFSPsShared neoantigens

Induction of tumor-specific T-cell responses (CD8+ and CD4+) by presenting non-self peptide sequences on MHC molecules to activate the adaptive immune system against dMMR/MSI-H tumor cells (Ballhausen et al., 2020; Mandal et al., 2019).