Bi-specific T-cell engagers (BiTEs) 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 (scFvs) 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.
Video Bi-specific T-cell engager
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.
Maps Bi-specific T-cell engager
Examples
Clinical trials
The following BiTEs are in clinical trials as of July 2010:
- Blinatumomab (MT103): for the treatment of non-Hodgkin's lymphoma and acute lymphoblastic leukemia; directed towards CD19, a surface molecule expressed on B cells
- Solitomab (MT110): for the treatment of gastrointestinal and lung cancers; directed towards the EpCAM antigen
Further research
Utilizing the same technology, melanoma (with MCSP specific BiTEs) and acute myeloid leukemia (with CD33 specific BiTEs) 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 (targeting HER2/neu), cetuximab and panitumumab (both targeting the EGF receptor), using the BiTE approach. BiTEs against CD66e and EphA2 are being developed as well.
References
Further reading
- Kufer, P; Lutterbüse, R; Baeuerle, PA (2004). "A revival of bispecific antibodies". Trends in Biotechnology. 22 (5): 238-44. doi:10.1016/j.tibtech.2004.03.006. PMID 15109810.
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