Recombinant T-cell Receptor Ligands for Treatment of Uveitis

DESCRIPTION (provided by applicant): Uveitis is a group of inflammatory eye diseases, often associated with an underlying autoimmune disease process. It is currently estimated that each year in the United States, from 17-52 out of every 100,000 persons will develop uveitis, totaling over 38,000 new cases per year. It is further estimated that 10% to 15% of the blindness in the United States is due to uveitis. Immune responses to ocular autoantigens play a central role in the pathogenesis of uveitis and are genetically controlled by specific human leukocyte antigen (HLA) loci. The goal of this project is to develop therapeutic drugs for the treatment of autoimmune uveitis that can control T cell immune responses characteristic of a subset of uveitic patients. This project is a collaborative work between OHSU and Virogenomics, a Portland biotechnology company that holds an exclusive license for Recombinant T-cell Receptor Ligands (RTLs) therapeutic technology. This new drug is a novel molecule consisting of the a1b1 domains of HLA-DR2 as a single chain that is linked to an antigenic peptide. RTLs have been found to inhibit T-cell responses in experimental models of multiple sclerosis, which has provided a basis for testing and applying RTLs in other autoimmune diseases, such as autoimmune uveitis. Our preliminary studies of treatment of autoimmune anterior uveitis (AAU) suggest a clinical application for RTLs in uveitic patients. The objective of this Phase I STTR application is to determine the effectiveness of RTLs in treating established acute and recurrent autoimmune uveitis in Lewis rats. These findings will provide rational basis for preclinical and Phase I clinical studies of the RTLs in uveitis patients. We propose the following specific aims: 1. To determine an effective treatment regimen for clinical rat AAU using RTLs. 2. To determine the abilities of RTLs to inhibit recurrent anterior and posterior uveitis in Lewis rats.