Major histocompatibility complex-RED frameshift peptide complex (MHC-RED-FSP)

The Major histocompatibility complex-RED frameshift peptide complex is a therapeutic target consisting of human leukocyte antigen (HLA) molecules presenting novel peptides derived from frameshift mutations in the IK gene (also known as RED). In cancers characterized by microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR), such as Lynch syndrome-associated colorectal and endometrial cancers, the IK gene frequently undergoes a -1 base pair deletion within a coding poly-A tract. This mutation generates a highly immunogenic, non-self C-terminal peptide sequence that is absent in healthy cells. These frameshift-derived neoantigens (FSNs) are processed and loaded onto MHC Class I or II molecules for presentation to the immune system. Because these mutations are shared across many patients with MSI-H tumors, the resulting pMHC complexes serve as ideal targets for 'off-the-shelf' cancer vaccines and T-cell receptor (TCR)-based therapies. Drugs targeting this complex aim to stimulate or provide T cells that specifically recognize the RED frameshift peptide, leading to the selective destruction of malignant cells while sparing normal tissue.

Other names

MHC-RED frameshift peptide complexHLA-presented RED frameshift neoantigenIK frameshift peptide-MHC complexProtein RED frameshift neoantigenShared frameshift neoantigen (FSN) from IK gene