RNA binding motif protein 14 frameshift-derived neoantigen presented on MHC (RBM14-fs-MHC)

The RNA binding motif protein 14 (RBM14) frameshift-derived peptide neoantigen presented on MHC is a tumor-specific target arising from somatic frameshift mutations in the RBM14 gene. These mutations are particularly prevalent in cancers with microsatellite instability (MSI-H), where the loss of DNA mismatch repair leads to frequent insertions or deletions in repetitive DNA sequences (PubMed: 30651630). The resulting frameshift generates a novel C-terminal peptide sequence that is entirely foreign to the host immune system. This neoantigen is processed and presented by Major Histocompatibility Complex (MHC) class I or II molecules, allowing for recognition by CD8+ or CD4+ T cells, respectively (PubMed: 28934463). Because the sequence is not expressed in healthy tissues, it serves as a high-quality target for precision immunotherapies, including neoantigen-based vaccines and TCR-engineered T-cell therapies. These therapeutic strategies aim to leverage the high immunogenicity of frameshift peptides to induce a robust anti-tumor immune response. Potential challenges include the heterogeneity of neoantigen expression and the potential for tumor cells to downregulate MHC molecules to evade immune detection.

Other names

RBM14 frameshift peptideRBM14 neoepitopeRNA binding motif protein 14 neoantigenCoAA frameshift antigen

Induction of T-cell mediated cytotoxicity against tumor cells presenting the RBM14 frameshift-derived peptide on MHC molecules.