Brachyury peptide–specific T-cell receptor (Brachyury-specific TCR)

Brachyury is a transcription factor that plays a critical role in mesoderm formation during embryonic development but is typically silenced in adult tissues. However, it is highly overexpressed in chordoma and various common epithelial cancers, where it promotes the epithelial-mesenchymal transition (EMT), contributing to tumor invasion and metastasis (Palena et al., 2007, Cancer Research). Brachyury peptide-specific T-cell receptors (TCRs) are synthetic or cloned receptors engineered to bind specifically to Brachyury-derived peptides presented by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01 (Hamilton et al., 2017, Oncotarget). In TCR-T cell therapy, these receptors are introduced into a patient's T-cells to enable the recognition and destruction of Brachyury-expressing malignant cells (NCT02858388, ClinicalTrials.gov). This therapeutic strategy targets a specific intracellular protein that is otherwise inaccessible to conventional antibody-based therapies, offering a precision medicine approach for aggressive and metastatic cancers. Clinical development of these TCRs focuses on treating patients with chordoma and other advanced solid tumors that have failed standard of care.

Other names

T-protein-specific T-cell receptorBrachyury-targeted TCRT-gene-specific T-cell receptorBrachyury-specific TCR

Engineered T-cell receptors recognize specific Brachyury-derived peptides (such as the WLLPGTSTV epitope) presented by Human Leukocyte Antigen (HLA) molecules on the surface of tumor cells, triggering T-cell activation and subsequent lysis of the cancer cell.