I’m not so much an antibody guy, but of course I’ve heard about catalytic antibodies. Catalytic antibodies bind, with the very high affinity that’s typical of many antibodies, to transition state molecules, stabilizing the transition state and facilitating the chemical reaction. They’ve been around for quite a while (I think the first, or at least first widely-announced, catalytic antibody1 was described in the mid-1980s) and a fair number of them have been created.
But as far as I know, catalytic antibodies remain a curiosity — a fascinating curiosity, but one without a lot of practical application. Although they can be custom-made and can have great specificity, as enzymes they tend to be really crappy (as you might expect), acting thousands or millions of times slower than “genuine” enzymes. Again, I’m no expert, but it seems that in spite of decades of promise, there hasn’t been much payoff; which is a shame, because the concept is so cool they deserve to make it big.2
Recently, though, there was a paper3 offering a catalytic antibody that actually was therapeutic in a real live animal model. Is this the one where promise actually follows through to reality?
The antibody was raised against a virulence factor, urease, of Helicobacter pylori, the ulcer-causing bacterium. (Urease helps neutralize the stomach acid, so it helps H. pylori colonize stomachs.) The antibody degraded urease reasonably well; and more remarkably, the light chain alone of the antibody was also able to degrade H. pylori urease. I don’t know how common this is for catalytic antibodies,4 but it strikes as potentially useful, since the light chain can be more readily synthesized and is probably more stable on its own.
The interesting part was that they treated mice with this — I think the first time catalytic antibodies have been used in vivo. They infected the mice with H. pylori, and then treated them with either the catalytic light chain in buffer, or with buffer alone (they should really have used a control light chain in buffer, though — in general this paper doesn’t strike me as terribly well-controlled when is comes to the animal work, but part of that may be the poor English throughout). The treated mice had about a third as many bacteria in their stomachs as did control mice, suggesting that the antibody actually did some good. Presumably it degraded urease in vivo as it does in vitro, and by inceasing stomach acidity helped reduce the bacterial survival.
This is still far, far from any kind of useful treatment, I think, but it’s a step forward.
- Pollack SJ, Jacobs JW, Schultz PG (1986) Selective chemical catalysis by an antibody. Science 234:1570-1573.[↩]
- If I’m wrong, by the way, and catalytic antibodies have achieved a toehold somewhere in medicine or industry, please let me know. As I say, I don’t follow this field all that closely.[↩]
- Hifumi, E., Morihara, F., Hatiuchi, K., Okuda, T., Nishizono, A., Uda, T. (2007). Catalytic Features and Eradication Ability of Antibody Light-chain UA15-L against Helicobacter pylori. Journal of Biological Chemistry, 283(2), 899-907. DOI: 10.1074/jbc.M705674200[↩]
- It’s not unique, because the authors say they had the same thing for a previous catalytic antibody they made[↩]