Regeneron's VEGF Trap.

Regeneron of Tarryton, New York, has turned the usual way of using antibodies as therapeutics on its head. To produce therapeutic agents that will mop up unwanted cytokines or growth factors, the company has developed a hybrid molecule called a 'Trap'. This is made from the stem of an antibody fused to two receptors for the target molecule. In this application, the antibody stem gives the molecule a long half-life in the circulation, while the receptors replace the variable regions. Traps therefore bind tightly to their target and can be given at infrequent intervals. Regeneron has created an interleukin-1 (IL-1) Trap that it hopes may be effective against rheumatoid arthritis, and is developing a dual IL-4/IL-13 Trap as a potential treatment for asthma and other allergies. A Trap for vascular endothelial growth factor (VEGF) is in clinical trials for the treatment of cancer by preventing the growth of blood vessels into solid tumours and non-Hodgkin's lymphoma. “Every time we compare them with a conventional antibody they have affinities two or three orders of magnitude higher,” says George Yancopoulos, Regeneron's chief scientific officer. Unlike antibodies, Traps will pick up every molecule that normally binds to the receptor, so the VEGF Trap will also bind the related growth factor PLGF.

Immunotoxins — antibodies linked to cytotoxic drugs — such as Wyeth's Mylotarg, have the potential to avoid some of the toxic side effects of traditional cancer chemotherapy by delivering the drug directly to the tumour cell. Seattle Genetics of Washington state is developing SGN-15, an antibody–drug conjugate composed of a mouse–human chimaeric monoclonal antibody chemically linked to the cytotoxic drug doxorubicin. This is currently in a phase II clinical trial for the treatment of lung cancer. The antibody binds to a Lewisy-related antigen expressed on many types of solid tumour. SGN-35, one of the company's second-generation immunotoxins now in preclinical trials, incorporates a potent synthetic drug and a novel chemical linkage that makes the molecule more stable in the blood.