BRAF V600E peptide-Major Histocompatibility Complex (BRAF V600E pMHC)

The BRAF V600E peptide-Major Histocompatibility Complex (pMHC) is a tumor-specific neoantigen formed by the presentation of a mutated BRAF protein fragment on the surface of cancer cells. The V600E mutation, a substitution of valine with glutamic acid, is a frequent oncogenic driver in melanoma, colorectal, and thyroid cancers (Davies et al., 2002). This mutation creates a unique peptide sequence that is absent in normal tissues, allowing the immune system to distinguish malignant cells from healthy ones when the peptide is presented by MHC molecules. Immunotherapeutic agents, such as the DPX-BRAF vaccine, are designed to stimulate the production of T cells that specifically recognize this pMHC complex (ClinicalTrials.gov NCT02293707). Upon recognition, these T cells exert targeted cytotoxic activity against the tumor, potentially overcoming the limitations of small-molecule BRAF inhibitors. The specificity of this target minimizes off-target toxicity, although therapeutic efficacy can be challenged by tumor-mediated immune evasion mechanisms like MHC downregulation (Somasundaram et al., 2014).

Other names

BRAF V600E neoantigenBRAF V600E-HLA complexMutated BRAF peptide-MHCBRAF V600E-derived peptide–MHC complex

Induction of antigen-specific cytotoxic T-lymphocyte (CTL) responses that recognize and lyse cells presenting the mutated BRAF V600E peptide on MHC molecules.