Mutant BRAF neoantigen peptide–major histocompatibility complex (MHC) (Mutant BRAF-MHC)

Mutant BRAF neoantigen peptide–MHC complexes are specialized molecular structures formed when mutated BRAF proteins, such as the common V600E variant, are processed into peptides and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules (Nature Communications, 2021, PMID: 33568656). These complexes are highly specific to tumor cells because the mutated peptide sequence is absent in the normal human proteome, making them ideal targets for precision immunotherapy (Journal of Clinical Investigation, 2015, PMID: 25503531). They are primarily recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T cells, which initiate a targeted immune attack against the cancer cell. Current therapeutic development focuses on engineering T cells with high-affinity TCRs specific for these BRAF neoantigens or using personalized vaccines to prime the endogenous immune system (Frontiers in Immunology, 2020, PMID: 32117311). This target is particularly significant in melanoma and other BRAF-driven cancers where traditional kinase inhibitors may face resistance issues. By targeting the presented neoantigen, these therapies offer a way to achieve durable responses through the immune system's specificity and memory.

Other names

BRAF V600E neoantigen-MHCBRAF-derived neoepitope-HLA complexMutant BRAF-HLA complexBRAF V600E-HLA-A*02:01

Recognition by T-cell receptors (TCRs) on cytotoxic T lymphocytes, leading to targeted cell lysis and cytokine release (Nature Communications, 2021, PMID: 33568656).