Trophoblast glycoprotein (5T4) peptide-MHC complex (5T4 pMHC)

Trophoblast glycoprotein, commonly known as 5T4, is a 72 kDa oncofetal antigen characterized by its leucine-rich repeat extracellular domain and is encoded by the TPBG gene (UniProt Q13641). It is highly expressed on the surface of various carcinomas, including colorectal, lung, and ovarian cancers, while maintaining very limited expression in normal adult tissues, making it an ideal candidate for targeted immunotherapy (PMID: 15623479). The target specifically involves 5T4-derived peptides, such as those restricted to HLA-A2, which are processed and presented on the Major Histocompatibility Complex (MHC) to be recognized by T-cell receptors (TCRs) (PMID: 11544010). In the tumor microenvironment, 5T4 expression is associated with increased cell motility and the epithelial-mesenchymal transition (EMT), contributing to metastatic potential and poor prognosis. Therapeutic interventions targeting this complex include cancer vaccines like TroVax (MVA-5T4), which induces a robust T-cell response against 5T4-expressing cells, and emerging TCR-engineered T-cell therapies (PMID: 21244194). By focusing on the peptide-MHC interface, these therapies aim to harness the precision of the adaptive immune system to selectively eliminate malignant cells while sparing healthy tissue.

Other names

5T4 oncofetal antigen-derived peptides presented on MHCTPBG peptide-HLA complex5T4-HLA-A2 complexWnt-activated inhibitory factor 1 peptide-MHC

Recognition of tumor-specific 5T4 peptides presented on Major Histocompatibility Complex (MHC) molecules by T-cell receptors (TCRs) to trigger a cytotoxic T-lymphocyte immune response against cancer cells.