Twist-related protein 1-specific T-cell receptor (Twist1-TCR)

Twist-related protein 1 (Twist1)-specific T-cell receptors (TCRs) are specialized immune receptors engineered to recognize and bind to specific peptide fragments of the Twist1 transcription factor presented by Major Histocompatibility Complex (MHC) molecules (UniProt: Q15672). Twist1 is a master regulator of the epithelial-mesenchymal transition (EMT), a biological process that enables cancer cells to gain migratory and invasive properties, leading to metastasis and increased resistance to conventional therapies (PubMed: 22496215). Since Twist1 is an intracellular protein, it cannot be targeted by traditional monoclonal antibodies; however, its processed peptides are displayed on the cell surface via MHC class I, making them accessible to CD8+ T cells equipped with these specific TCRs (PubMed: 31164418). These receptors are primarily utilized in TCR-engineered T-cell (TCR-T) therapy, where a patient's own T cells are modified to express the Twist1-specific TCR to selectively eliminate tumor cells expressing the EMT phenotype. Clinical and preclinical studies have focused on HLA-A*02:01-restricted epitopes, demonstrating that these TCRs can induce potent cytotoxic responses against various solid tumors, including breast and lung cancers (PubMed: 28811331). While Twist1 is highly expressed in many malignancies, its expression in healthy adult tissues is generally low, though potential risks include off-target effects on mesenchymal stem cells or interference with normal tissue repair processes.

Other names

Twist1-specific CD8+ T-cell receptorTwist1-reactive T-cell receptorTwist-related protein 1-specific TCR

Binding to Twist1 peptide-MHC class I complexes on the surface of tumor cells, triggering T-cell activation, cytokine release, and cytotoxic degranulation (PubMed: 31164418).