Medicine Prelim, University at Buffalo Radiation-Oncology, University of Minnesota, Minneapolis
Oral IL10 nanoparticles alleviate polyposis via site-specific neutralization of pathogenic T-regulatory cells. (Completed 2013)
The immune-modulatory cytokine interleukin-10 (IL10) is essential for maintaining immune homeostasis at mucosal surfaces. The therapeutic potential of applying IL10 towards the treatment of inflammation-driven diseases has, however, been limited by both an incomplete understanding of IL10 biology and an inability to locally target IL10 to mucosal surfaces in a specific and sustainable fashion.
My thesis work utilized bio-polymer nanotechnology to show that orally-administered IL10 formulations can successfully recondition the intestinal immune system and ameliorate established colitis. Utilizing the APCmin mouse model of spontaneous gastrointestinal polyposis, our mechanistic studies revealed the efficacy of therapy to be partially dependent on the conditioning effect of IL10 upon T-regulatory cells. In situ reprogrammed T-regulatory cells regained their native immunosuppressive potential and became more efficient at controlling intestinal inflammation. Oral IL10 nanoparticles alleviated constitutional symptoms, corrected fatal anemia and extended natural lifespan in our experimental animals.
Translation of our basic scientific discoveries into the clinical setting has revealed an important role for the immune system in the development of disease in patients with inherited polyposis syndromes (Familial Adenomatous Polyposis and Hereditary Nonpolyposis Colorectal Cancer). In collaboration with partners from both academia and industry, ongoing studies are attempting to explore the broader applicability of nanoparticle biologics in the treatment of a wide array of immune-pathologic disease.
Nejat Egilmez, PhD