"One thing I like about this work," Brent Iverson told BioWorld Today, "is that it is very practical on one level - how do you make cheaper antibodies? But there's also a basic science component of reaching into the unknown."

Iverson was referring to a study published by his own laboratory and others at the University of Texas at Austin and the Southwestern Foundation for Biomedical Research in San Antonio in the December 2005 issue of Infection and Immunity that investigates the use of antibody fragments for passive immunization against anthrax.

In their studies, the scientists used an antibody fragment that they had identified in previous work. Engineered to have higher affinity than the natural antibody it is based on, the antibody fragment recognizes the protective antigen toxin or PA toxin component of anthrax. The fragment is licensed to Pine Brook, N.J.-based Elusys Therapeutics Inc., which two months ago began Phase I trials of Anthim, a whole antibody including the fragment. (See BioWorld Today, Oct. 4, 2005.)

So far, the whole antibody "is working very well," Iverson said. "We do not expect that this [fragment] would be any more effective."

What the new results might show is a cheaper way of getting the same effect. The standard operating procedure for making monoclonal antibodies is to clone the regions of the antibody that are involved in antigen binding into E. coli for mass production. However, use of those fragments alone has several limitations. For that reason, the fragments are usually put back onto an antibody scaffold; the scaffold cannot be produced in bacteria and so must be made in mammalian cell culture instead.

When whole antibodies are given, they not only bind the antigen (in this case, PA toxin) but also activate a person's own immune defense to help pitch in against the invader via so-called Fc receptors. The Infection and Immunity study was designed to test whether antibody fragments that do not stimulate the immune system are sufficient to protect against anthrax. Iverson said that the main question the study addressed was, "What do we lose by not having a whole antibody?" And the answer is, apparently, not much.

In their study, instead of mounting the cloned binding fragments back onto an antibody scaffold, the scientists conjugated them to polyethylene glycol. Adding polyethylene glycol to molecules, including antibody fragments, is a well-established technique and commercially available from San Carlos, Calif.-based Nektar Therapeutics Inc. The polyethylene glycol itself is inert, but the combined molecule is relatively large and has a much longer half-life in the body.

In the current study, PEGylation gave the fragments a half-life that was comparable to that of whole antibodies, without interfering with the binding of the antibody to PA toxin. An unexpected finding was that despite the fact that in animal studies, even though the PEGylated antibody fragment did not stimulate the immune system, it cured some of the guinea pigs. While inhaling anthrax spores killed the control group within a few days, 50 percent to 60 percent of animals treated prohpylactically with the PEGylated antibody fragment not only survived, but also showed no evidence of disease and only trace amounts of anthrax bacteria in their bodies after two weeks.

Iverson termed that "a big surprise," because it cannot be explained by the antibody's known binding to PA toxin. When anthrax spores are inhaled, they need to germinate to produce PA toxin in the first place; if the antibody were binding solely to the PA toxin, that would not stop the bacteria from reproducing and continuing to colonize their host.

"Protective antigen is doing double duty," Iverson said. In the experiments, the antibody bound to the antigen and cleared it out of the body. But in addition, "it is somehow keeping the spores from germinating."

Iverson pointed out that passive immunization was once the state-of-the-art treatment, and if his results hold up in the clinic, it might become so again. "In a lot of ways," Iverson said, "this is back to the future."

The Iditarod dog sled race, for example, commemorates the emergency delivery of diphtheria antiserum from Anchorage to Nome, Alaska, in 1925. Iverson said he "first learned that from a Walt Disney movie." He learned it from the animated film "Balto," in which a half-wolf, half-husky goes from outcast to hero by leading the dog sled team that brings the serum to Nome. Who says commercial films have no educational value?