Frameshift-derived neoantigen peptide (FSP)

Frameshift-derived neoantigen peptides (FSPs) are a class of highly immunogenic tumor-specific antigens that arise from insertions or deletions (indels) in the genome that shift the open reading frame of a gene. This shift results in the translation of entirely novel, non-self amino acid sequences that are absent from the normal human proteome, making them ideal targets for cancer immunotherapy as they bypass central thymic tolerance (PMID: 31534227, PMID: 33073218). These peptides are particularly prevalent in cancers characterized by microsatellite instability (MSI) or DNA mismatch repair deficiency (dMMR), such as Lynch syndrome-associated colorectal and endometrial cancers (PMID: 32814071). In a therapeutic context, FSPs are utilized as the primary components of personalized or "off-the-shelf" cancer vaccines designed to prime the patient's immune system to recognize and destroy malignant cells. Because frameshift mutations often occur at predictable "hotspots" in MSI-H tumors, shared FSPs can be incorporated into universal vaccine formulations like Nous-209 (PMID: 36253470). When administered, these peptides are processed and presented by Major Histocompatibility Complex (MHC) molecules, triggering robust CD8+ cytotoxic T-cell and CD4+ helper T-cell responses. This targeted approach minimizes off-target toxicity while providing a potent mechanism for overcoming tumor-induced immunosuppression (PMID: 28978771).

Other names

Frameshift neoantigenIndel-derived neoantigenFS-neoantigenFrameshift-derived peptideShared frameshift peptide

Induction of a specific T-cell mediated immune response (CD4+ and CD8+) against tumor cells expressing novel, non-self peptide sequences derived from genomic frameshift mutations.