Lay Summary

Proposal No. IBD-0123
Principal Investigator:  Pieter Rottiers, Ph.D. (replacement PI); Claude Cuvelier, M.D., Ph.D. (original PI)
Current Applicant Organization:  Flanders Interuniversity Institute for Biotechnology vzw (Ghent, Belgium)
Original Applicant Organization:  Ghent University (Belgium)
Project Title:  Treatment of experimental colitis by camelid antibody fragments:  local delivery by genetically engineered lactococci administration and evaluation of their therapeutic potential
Period of Award:  July 1, 2004 - June 30, 2006

Crohn's disease (CD) is a chronic disorder that causes inflammation of the digestive tract caused by an inappropriate response of the body's immune system.  The treatment of CD with antibodies against tumor necrosis factor-alpha (TNF-α) has been shown to be promising and has become an approved therapy in the U.S.A. and Europe.  TNF-α is a pro-inflammatory protein produced by white blood cells and is thought to be responsible for many of the clinical symptoms in CD.  Although intravenous administration of this antibody has been shown to be a successful therapy in many patients, the treatment is costly and its effect is temporal and associated with adverse effects.  At the moment, other antibodies are being evaluated for their potential beneficial effect in treatment of CD, including antibodies directed against IFN-γ.

This project aims at evaluating the use of TNF-α and IFN-γ neutralizing camelid antibodies expressed by food grade bacteria (Lactococcus lactis) to treat CD.  Camelid antibodies are much more stable than conventional antibodies and can withstand harsh conditions such as those encountered in the gastrointestinal tract.  The L. lactis strains will be used to deliver the TNF-α and IFN-γ neutralizing camelid antibodies directly to the gut, producing high drug concentrations at the site of inflammation and fewer systemic side effects. 

We previously reported that administration of L. lactis delivering immunomodulating proteins at the intestinal mucosa is effective in treating colitis in animal models for CD.  By combining the unique features of the camelid antibodies and the L. lactis-mediated delivery system, we hope to develop a new, cost-effective approach of local immune therapy to treat patients with CD.