Establishment of a novel therapy of Inflammatory bowel disease by inducible oral tolerance

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For years medical researchers have strived to develop selective immunotherapies that could specifically ameliorate pathogenic immune responses without immunocompromising the patient. Blockade of many known receptors on T cells can inhibit the initiation of immune responses. However, this approach is problematic in that it is not possible to predict the onset of disease in patients. Current immunotherapies are unsatisfactory for sporadic exacerbating-type of diseases such as multiple sclerosis and inflammatory bowel disease (IBD), because they require either long-term treatment or acute treatment with high-dose immunosuppressants. With regard to this issue, the inducible and inflammatory site-specific molecule, inducible co-stimulator (ICOS), may be particularly useful as an ideal targeting molecule for the strategy of treatment of human IBD patients. First, we found significantly increased expression of ICOS on T cells in inflamed colon from both IBD patients and colitic mice, but not in uninflamed mucosa and in periphery. Based on these results, we demonstrated anti-ICOS mAb ameliorated chronic murine experimental colitis when administrated either early or late after induction of colitis. In addition, we are under investigation to establish a bacterium genetically enginneered to secrete soluble costimulatory molecules to inhibit physiological costimulatory pathway for a novel therapy of IBD.