Day 1 :
University of Louisville, USA
Keynote: Specific targeting of pathogenic T-cells for the induction of tolerance to pancreatic islet grafts for the treatment of type-1 diabetes
Time : 09:35-10:00
Haval Shirwan is a Dr. Michael and Joan Hamilton Endowed Chair in Autoimmune Disease, Professor of Microbiology and Immunology, Director of Molecular Immunomodulation Program at the Institute for Cellular Therapeutics. He has completed his Graduate studies from the University of California in Santa Barbara, CA and Postdoctoral studies from California Institute of Technology in Pasadena, CA. He has joined the University of Louisville in 1998 after holding academic appointments at various academic institutions in the United States. His research focuses on the modulation of immune system for the treatment of immune-based diseases with particular focus on type-1 diabetes, transplantation and development of prophylactic and therapeutic vaccines against cancer and infectious diseases. He is an Inventor on over a dozen of worldwide patents, Founder and CEO/CSO of FasCure Therapeutics, LLC, widely published, organized and lectured at numerous national/international conferences, served on study sections for various federal and non-profit funding agencies and is on the Editorial Board of a dozen of scientific journals. He is Member of several national and international societies and recipient of various awards.
Type-1 diabetes (T1D) is an autoimmune disease initiated and perpetuated by T-cells targeting various auto antigens. Insulin treatment as standard of care is often ineffective in preventing recurrent hyperglycemic episodes with long-term undesired adverse effects. Transplantation of pancreatic islets as a source of beta cells producing insulin has proven effective in improving metabolic control/quality of life and preventing severe hypoglycemia in patients with T1D. Immune rejection of the transplanted islets is presently being controlled by chronic immunosuppression that is not only ineffective in controlling rejection but also has various side effects. Therefore, novel approaches that control rejection in the absence of chronic immunosuppression will have significant impact on the field of islet transplantation. In as much as T-cells are critical to graft rejection, we have developed an effective immunomodulatory approach based on the novel form of immune ligands to target pathogenic T-cells for physical elimination while simultaneously expanding protective Treg cells. The application of this concept to allogeneic and xenogeneic islet transplantation will be discussed.
Albany Medical College, USA
Keynote: Anti-angiogenic and Pro-apoptotic Activity of Nano-diamino-tetrac (Nanotetrac) initiated at a Cell Suface Target on Integrin αvβ3
Time : 10:30-11:00
Paul J Davis has obtained his MD degree at Harvard Medical School and his Clinical and Research Training at Albert Einstein College of Medicine; NIH. He is a Professor of Medicine at Albany Medical College (Albany, NY USA) and a Former Chair of the Department of Medicine at Albany. He has Co-Authored 250 refereed papers and he and his colleagues described the cell surface receptor for thyroid hormone. He and co-workers at the Albany College of Pharmacy have generated nanopharmaceuticals of thyroid hormone and hormone analogues that modulate angiogenesis and tumor cell proliferation and viability.
Integrin αvβ3 is concentrated and activated on the surface of tumor cells and dividing endothelial cells where it is critical to cell-cell and cell-extracellular matrix protein interactions and to function of cell surface vascular growth factor receptors. Exploration of the functions of a receptor for thyroid hormone and hormone analogues on the integrin has linked hormone analogues to regulation of expression of genes relevant to angiogenesis to differential regulation of apoptosis (pro- and anti-apoptosis) and to repair of double-strand DNA breaks. Tetraiodothyro-acetic acid (tetrac) is a naturally-occurring deaminated analogue of L-thyroxine (T4) that, when covalently bound to a nanoparticle that precludes its cellular uptake acts exclusively at αvβ3 via a variety of signal transducing kinases and other mechanisms as an anti-cancer/anti-angiogenesis agent. We report here the action of systemic nanoparticulate tetrac (Nano-diamino-tetrac, NDAT or Nanotetrac) on human glioblastoma (U87MG) xenograft size and histology. Ten days’ daily subcutaneous treatment of tumor-bearing nude mice with NDAT (1 mg tetrac-equivalent/kg/day) resulted in a 38% decrease in tumor volume in situ and 47% decrease in tumor weight at sacrifice (p<0.01 vs. control). Blinded histopathologic review of tumors from control and treated animals has revealed essentially complete loss of vascularity without hemorrhage and consequent 5-fold increase in necrotic cells in drug-exposed tumors. There was 4.5-fold increase in apoptotic cells in treated tumors. Changes were significant at p<0.01. NDAT is a novel nanopharmaceutical that acts exclusively on cancer and endothelial cell surfaces to induce apoptosis and systematic devascularization with necrosis.