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Novel antitoxin strategy developed using 'tagged binding agents'
Date:2/25/2010

a 2002 breakthrough at the University of California at San Francisco, where scientists combined three monoclonal antibodies against Botulinum toxin that attached to different parts of the toxin molecule. Including three different antibodies dramatically increased the potency compared to fewer antibodies and prevented intoxication even following high-dose exposure. However, developing, producing, and stockpiling three different monoclonal antibodies against each toxin type is very expensive.

Instead of using three antibodies, the Tufts approach uses three small binding agents to direct a single monoclonal antibody to multiple sites on the biomolecule being targeted for clearance. The type of binding agents used can be selected from many scaffolds developed for commercial therapeutic applications (e.g. nanobodies, aptamers, darpins, FN3, microbodies, etc). These binding agents can be rapidly identified and improved using modern technologies and generally have excellent commercial production and product shelf-life properties. The single anti-tag monoclonal antibody can also be selected to have optimal isotype and commercialization properties.

What's more, the binding agents can be produced with more than one tag, which enables them to direct more antibodies to the toxinand synergistically improve target clearance from the body. Many binding agent scaffolds can be produced as functional multimers so that the different binding agents could be produced as "beads on a string," leading to a single molecule that targets one, or even several, biomolecules for clearance from the body.

Using this approach, the researchers say, one would only need to create new binding agents, not new antibodies, to create a therapy to clear a toxin from the bodypaving the way for new therapies that combat toxins ranging from animal venom to bioterrorist agents such as ricin. Tufts researchers are currently targeting Shiga toxin and C. difficile along with other ty
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Contact: Tom Keppeler
tom.keppeler@tufts.edu
508-839-7910
Tufts University, Health Sciences
Source:Eurekalert

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