Amgen originally encountered the BiTE technology in a partnering deal it entered with Micromet on solid tumors last year. Several other firms have ongoing BiTE-based drug development collaborations with Micromet, including Paris-based Sanofi; Boehringer Ingelheim of Ingelheim, Germany; Berlin-based Bayer Schering Pharma; and London-based AstraZeneca's MedImmune unit. “That in itself gives a pretty good indication of the excitement among our big pharma peers for this platform,” says David Chang, vice president of global development for oncology at Thousand Oaks, California–based Amgen.
BiTE mAb fragments, unlike classic antibodies, possess two different minimal antigen-binding domains from two single-chain Fvs (scFvs) arranged in tandem on a polypeptide chain. The molecules are engineered to bind simultaneously a T-cell antigen and a tumor-associated antigen expressed by a cancer cell. This structural arrangement over-rides the normal inability of T cells to recognize antibodies directly (because of their lack of Fc gamma receptors) and thereby leads to a cytotoxic T-cell response directed against a tumor bearing the antigen presented on the BiTE molecule. Blinatumomab targets both CD19, a B-cell antigen, and CD3, a component of the TCR complex on the surface of T cells, which is essential for T-cell activation. “It's pioneering technology based on a simple, elegant concept,” enthuses Amgen's Chang. “You can view it as turbocharging immunotherapy.”
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