Brachyury protein (TBXT)

Brachyury, encoded by the TBXT gene, is a member of the T-box family of transcription factors and plays a critical role in posterior mesoderm formation and notochord development during embryogenesis (UniProt P27037). While its expression is largely absent in healthy adult tissues, it is aberrantly reactivated in various human malignancies, most notably chordoma, where it serves as a definitive diagnostic marker and oncogenic driver (PMID: 24501019). Beyond chordoma, Brachyury is a master regulator of the epithelial-mesenchymal transition (EMT), a process that enables tumor cells to lose their epithelial characteristics and gain migratory, invasive, and stem-like properties, leading to metastasis and resistance to conventional chemotherapy and radiation (PMID: 20802021). Because Brachyury is an intracellular protein, it is primarily targeted through immunotherapeutic approaches, such as viral-vector (e.g., MVA-BN-Brachyury) or yeast-based vaccines (e.g., GI-6301), which are designed to stimulate a T-cell-mediated immune response against tumor cells presenting Brachyury-derived peptides on their surface (National Cancer Institute). Clinical development focuses on using these vaccines to treat advanced solid tumors and chordoma, often in combination with immune checkpoint inhibitors to enhance therapeutic efficacy.

Other names

T-box transcription factor TT-box proteinTBrachyury homologT-box transcription factor Brachyury

Induction of antigen-specific T-cell mediated cytotoxicity against cells expressing the Brachyury protein via vaccine-delivered epitopes presented on MHC class I molecules.