University of Toronto Background
Deregulated balance of the immune system strongly contributes to the development of chronic inflammatory conditions, like inflammatory bowel disease (IBD). A critical cellular element in sustaining immune and tissue homeostasis are mononuclear phagocytes (MNP), hematopoietic, migratory cells with superior capability to engulf and kill microbes, as well as priming and sustaining adaptive immune responses. Convincing animal research and accumulating evidence in humans suggest that these cells are fundamental in determining whether the immune system is activated or remains tolerant towards microbes. Key to their regulation, particularly in the intestinal tract, is a particular cytokine, hereafter denoted as “Cytokine X”. Every 5th patient diagnosed with Crohn’s disease (CD) displays neutralizing autoantibodies (AuABs) against Cytokine X reducing its potential as a therapeutic. In engineering mechanisms involving Cytokine X to evade these antibodies, effective treatments against Crohn’s disease may be developed.
Inventors at the University of Toronto have genetically engineered Cytokine X to be a more effective therapeutic. They have found that mutating selective residues, resulting in altered glycosylation motifs while retaining normal biological function, facilitate the evasion from Cytokine X AuAB-mediated neutralization in CD patients. The investigators further identified that Cytokine X AuABs are a reliable early serological marker preceding the diagnosis of CD by years. Serological recognition of Cytokine X AuABs further indicates CD severity and complications of disease at the time of diagnosis. This invention generates a cytokine and serological diagnosis tool that is suitable for therapeutic use in all CD patients including those with Cytokine X AuAB. This invention opens the door towards a true personalized diagnostic and therapeutic approach for the improvement and possible prevention of CD.
Stage of Development
Elevated levels of autoantibodies against Cytokine X were detected in the serum of Crohn’s disease patients () demonstrating diagnostic potential. Furthermore, genetically engineered Cytokine X proteins have been synthesized and their therapeutic potential is being tested for use in Crohn’s disease.
Diagnostic / Prognostic
~ 40% of Crohn’s disease patents can be diagnosed and even identified years in advance of disease onset
Genetic modifications to Cytokine X allow it to evade the immune system and exert its preventive function even in CD patients with Cytokine X autoantibodies
Diagnosis and treatment of Crohn’s Disease
Co-development of the technology via sponsored research and/or licensing of technology.
UofT ID: P2182