Frameshift peptide neoantigen-Major Histocompatibility Complex (FSP-MHC)

Frameshift peptide neoantigen-Major Histocompatibility Complex (FSP-MHC) refers to the presentation of novel peptides, generated by frameshift mutations, on the surface of cells via MHC molecules (PMID: 31534227). These mutations, often caused by defects in DNA mismatch repair (dMMR) leading to microsatellite instability (MSI), result in entirely new amino acid sequences that are highly immunogenic because they are absent from the normal human proteome (Nature, 2017). Because these "non-self" peptides are not subject to central immune tolerance, they serve as potent targets for the immune system (PMID: 28933433). Therapeutic strategies targeting FSP-MHC complexes include cancer vaccines like Nous-209 and TCR-based therapies designed to stimulate or provide T-cells that specifically recognize these complexes (NCT04041310). These targets are particularly relevant in MSI-H colorectal, gastric, and endometrial cancers, where shared frameshift mutations across patients allow for the development of "off-the-shelf" immunotherapies (PMID: 33077394). The presentation of these complexes on both tumor cells and antigen-presenting cells (APCs) is crucial for the priming and effector phases of the anti-tumor immune response.

Other names

Frameshift-derived neoantigensFSP-HLA complexesMicrosatellite instability-associated neoantigensShared neoantigensFSP-MHC complexes

Induction of T-cell mediated cytotoxicity through the recognition of frameshift-derived neoepitopes presented on MHC Class I or II molecules (PMID: 31534227).