Tumor-specific frameshift neoantigen (FSN) (FSN)

Tumor-specific frameshift neoantigens (FSNs) are novel peptides generated by frameshift mutations, such as insertions or deletions (indels) in coding microsatellites, which shift the translational reading frame. These mutations are a hallmark of cancers with microsatellite instability (MSI) caused by a deficient DNA mismatch repair (dMMR) system (PubMed: 32603455). Because FSNs possess amino acid sequences entirely distinct from the normal human proteome, they are highly immunogenic and bypass central immune tolerance (PubMed: 28930647). These peptides are processed and presented by Human Leukocyte Antigen (HLA) molecules on the surface of tumor cells and antigen-presenting cells, where they serve as targets for CD8+ and CD4+ T cells. Therapeutic strategies, including "off-the-shelf" vaccines like Nous-209 and personalized neoantigen vaccines, aim to stimulate a robust anti-tumor immune response specifically against these neoepitopes (PubMed: 30395155). This approach is particularly relevant for MSI-H colorectal, gastric, and endometrial cancers, offering a potential synergy with immune checkpoint inhibitors.

Other names

Frameshift peptide (FSP)MSI-associated neoantigenFrameshift-derived neoantigenIndel-derived neoantigenTumor-specific frameshift neoantigen peptides presented by HLA molecules

Induction of a specific T-cell mediated immune response against tumor cells presenting frameshift-derived peptides via HLA Class I and II molecules.