BRAF V600E-specific T cell receptor (BRAF V600E TCR) (BRAF V600E TCR)

The BRAF V600E-specific T cell receptor (TCR) is an engineered or naturally occurring immune receptor designed to recognize the V600E mutation in the BRAF protein, a common oncogenic driver in various malignancies including melanoma and colorectal cancer (Veatch et al., 2018, J Clin Invest). This TCR is MHC-restricted, meaning it only identifies the mutant BRAF peptide when it is presented on the cell surface by specific Human Leukocyte Antigen (HLA) molecules, most frequently HLA-A*02:01 (Schuster et al., 2017, Cancer Immunol Res). In the context of adoptive cell therapy, patient-derived T cells are genetically modified to express this specific TCR, enabling them to selectively target and eliminate cancer cells harboring the BRAF V600E mutation while sparing healthy cells that lack the mutation. This approach leverages the high specificity of neoantigen recognition to provide a potent, personalized immunotherapy that can overcome the limitations of traditional BRAF inhibitors, such as acquired resistance (NCT05292859). The development of these TCRs represents a significant advancement in targeting intracellular oncogenic drivers that are otherwise inaccessible to conventional antibody-based therapies.

Other names

MHC-peptide–restricted T cell receptors specific for BRAF V600E neoantigenBRAF V600E-restricted T-cell receptorBRAF V600E neoantigen-specific TCRAnti-BRAF V600E TCR

The TCR specifically recognizes the BRAF V600E mutant peptide (typically the GLPRKISSV decamer) when it is processed and presented by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01, on the surface of tumor cells (Veatch et al., 2018, J Clin Invest). Upon binding to this peptide-MHC complex, the TCR triggers a signaling cascade through the CD3 complex, leading to T cell activation, proliferation, and the release of cytotoxic molecules such as perforin and granzymes, as well as pro-inflammatory cytokines like IFN-gamma and TNF-alpha, which collectively induce apoptosis in the target cancer cell (Schuster et al., 2017, Cancer Immunol Res).