Tetanus toxoid-specific T cell receptor (TT-TCR)

The Tetanus toxoid-specific T cell receptor (TT-TCR) is a specialized immune receptor found on memory T cells that recognizes peptides derived from the tetanus toxoid (TT) protein when presented by Major Histocompatibility Complex class II (MHC-II) molecules. In a novel cancer immunotherapy context, this receptor is leveraged to target tumor cells that have been 'infected' or loaded with TT protein using attenuated bacterial vectors like Listeria monocytogenes. Because most individuals have been vaccinated against tetanus, they possess a pre-existing pool of memory T cells equipped with these TCRs. When the bacterial vector delivers TT to the immunosuppressive tumor microenvironment, the tumor cells present TT peptides, effectively 'flagging' themselves for destruction by the circulating TT-specific memory T cells. This strategy bypasses the need to identify specific tumor-associated antigens and overcomes tumor-induced immune suppression by utilizing a potent, recall-based immune response. Research has demonstrated that this interaction can significantly reduce tumor burden and metastasis in various preclinical models of pancreatic and other solid cancers.

Other names

Tetanus toxoid-specific TCRTT-specific T-cell receptorTetanus toxoid-reactive T cell receptor

The therapeutic approach utilizes a weakened bacterium (e.g., Listeria monocytogenes) to deliver tetanus toxoid (TT) protein directly into tumor cells. Once inside, the TT protein is processed and its peptides are presented on the cell surface via MHC class II molecules. This allows pre-existing memory T cells, generated through prior tetanus vaccinations, to recognize the tumor cells via their TT-specific T cell receptors (TT-TCRs) and initiate a targeted cytotoxic immune response against the tumor.