Genmab Provides Insights into IgG4 Antibodies
- Category: Antibodies
- Published on Sunday, 16 September 2007 04:00
- Hits: 2855
COPENHAGEN, Denmark | September 13, 2007 | Genmab A/S (OMX: GEN) announced today its scientists have discovered the basis for the instability of human IgG4 antibodies underlying their biological role in the immune system. In pre-clinical studies, Genmab discovered that IgG4 antibodies are dynamic and unstable molecules that naturally exchange their target-binding arms with other IgG4 molecules. This exchange leads the antibody to essentially become bispecific with the potential ability to bind to two different targets. However, the IgG4 antibodies usually do not bind to two different targets simultaneously in vivo.
This exchange of target-binding arms underlies the anti-inflammatory activity seen with IgG4 antibodies and may lead to a dampening effect on inflammatory reactions in certain conditions such as allergies or autoimmune disease. These dynamic and unstable properties make IgG4 antibodies unpredictable and thus unfavorable for human therapeutic use, in spite of their potential advantage in treating diseases for which effector function is not desired.
These findings will be published in the journal Science on September 14. The studies were performed in collaboration with scientists at Sanquin Research, Amsterdam and the University of Maastricht, the Netherlands.
“These insights into the mechanisms of human IgG4 antibodies are what led Genmab to develop the UniBody™ technology platform,” said Prof. Jan G. J. van de Winkel, Chief Scientific Officer at Genmab. “By removing the hinge region of the IgG4 antibody molecule, we have created a small, stable and inert half-molecule with a long half-life called UniBody which may provide effective treatments for certain types of cancer and autoimmune disease.”