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
|Contact: Tom Keppeler|
Tufts University, Health Sciences