We learned in high school and/or undergrad biology that one antibody would bind to one antigen. This is what makes our immune system so effective: antibodies bind with high affinity to foreign proteins or other molecules. Not only that, but those antibodies are specific: they would bind only to a specific site on the foreign protein (epitope) and fitting in it like a key in a lock. They business end of the key (antibody) is called the paratope.
A group at Genentech designed an antibody whose paratope binds two completely different targets. Human epidermal growth factor 2 (HER2) and Vascular Endothelial Growth Factor (VEGF). Both proteins are cancer therapy targets, and both are targets of antibody therapy of two different engineered antibodies. Jenny Bostrom and her colleagues at Genentech have designed one antibody that binds both proteins. They used a phage display library starting from a HER2- binding antibody, and screened for an antibody that maintained HER2 binding, but in addition bound VEGF. Both proteins were bound with a high affinity. They actually bind competitively to the binding site, so the antibody cannot bind both VEGF and HER2, only one or the other.
Why bother doing that if we already have two antibodies, each binding its target epitope with a hight affinity? For therapeutic purposes, it is better to dose with one antibody than with a combination therapy. Combination therapies can be expensive, and their outcomes are unclear; sometimes the clinical outcome could be worse.
One interesting question this study raises is an evolutionary one. Could such antibodies exist naturally? Could we have evolved antibodies that bind two completely different epitopes? When we use antibodies in the lab, we tend to screen against those that are promiscuous: bind more than one epitope. But maybe such antibodies do exist? I’ll admit I am less than well-versed in immunology, so anyone who knows anything about this is welcome to comment. Would such antibodies increase their organsm’s fitness? We do know that one line of the body’s defence against against cancer is immunological, so could we have a mechanism generating such “two-for-one” antibodies against cancer, or pathogens?
Bostrom, J., Yu, S., Kan, D., Appleton, B., Lee, C., Billeci, K., Man, W., Peale, F., Ross, S., Wiesmann, C., & Fuh, G. (2009). Variants of the Antibody Herceptin That Interact with HER2 and VEGF at the Antigen Binding Site Science, 323 (5921), 1610-1614 DOI: 10.1126/science.1165480