Bi-specific T-cell engager


Bi-specific T-cell engagers are a class of artificial bispecific monoclonal antibodies that are investigated for the use as anti-cancer drugs. They direct a host's immune system, more specifically the T cells' cytotoxic activity, against cancer cells. BiTE is a registered trademark of Micromet AG.
BiTEs are fusion proteins consisting of two single-chain variable fragments of different antibodies, or amino acid sequences from four different genes, on a single peptide chain of about 55 kilodaltons. One of the scFvs binds to T cells via the CD3 receptor, and the other to a tumor cell via a tumor specific molecule.

Mechanism of action

Like other bispecific antibodies, and unlike ordinary monoclonal antibodies, BiTEs form a link between T cells and tumor cells. This causes T cells to exert cytotoxic activity on tumor cells by producing proteins like perforin and granzymes, independently of the presence of MHC I or co-stimulatory molecules. These proteins enter tumor cells and initiate the cell's apoptosis.
This action mimics physiological processes observed during T cell attacks against tumor cells.

Examples

Clinical trials

The following BiTEs are in clinical trials :
Utilizing the same technology, melanoma and acute myeloid leukemia can be targeted. Research in this area is currently ongoing. Another avenue for novel anti-cancer therapies is re-engineering some of the currently used conventional antibodies like trastuzumab, cetuximab and panitumumab, using the BiTE approach. BiTEs against CD66e and EphA2 are being developed as well.