Research Project
6137294
Our preliminary investigations have demonstrated that delivery of self peptide on genetically engineered immunoglobulin (Ig) vehicles increases peptide presentation to T cells by 100-1000 fold relative to free peptides. Furthermore, intraperitoneal injection of the self peptide-Ig chimera into mice with ongoing experimental allergic encephalomyelitis (EAE) substantially ameliorates the severity of this T cell-mediated autoimmune disease induced by a single predefined immunodominant peptide. We propose to extend these studies to assess the efficacy of such constructs in multiple epitope triggered EAE which would better model the human multiple sclerosis (MS). Subsequently, the feasibility of this strategy will be tested during different stages of EAE progression. Finally, we would like to explore whether delivery of these constructs to the respiratory mucosa could lead to equivalent or improved efficacy. To this end we propose to incorporate the Ig constructs into a novel lipid based particle delivery vehicle, Pulmospheres, These investigations will provide key information for proceeding to Phase II preclinical studies in non-human primates. PROPOSED COMMERCIAL APPLICATIONS: The goal of this work is to broaden the therapeutic benefit of modulation of autoreactive T cells in autoimmune disease, specifically multiple sclerosis, by developing methods to induce broad-based modulation of aggressive T cells. This work will lead to proof of concept studies in out- bred nonhuman primates where specific T cell epitopes are not as well defined and multiple epitopes may contribute to disease.
