Day 1 :
Case Western Reserve University School of Medicine, USA
Keynote: Matrix metalloproteinase-9 (MMP-9) production is increased by recombinant human interleukin-6 and recombinant human tumor necrosis factor-oo3B1; in immortalized human chondrocyte cell linesα
Time : 09:00-09:25
Charles J Malemud received the PhD from George Washington University in 1973 and completed postdoctoral studies at the State University of New York at Stony Brook in 1977. He is Professor of Medicine & Anatomy in the Division of Rheumatic Diseases and Senior Investigator in the Arthritis Research Laboratory at Case Western Reserve University School of Medicine. He has published more than 200 papers and reviews primarily in the field of chondrocyte biology. He is on the editorial board of several rheumatology, immunology and musculoskeletal journals and is Editor-in-Chief of the Journal of Clinical and Cellular Immunology.
The degradation of articular cartilage extracellular matrix proteins by matrix metalloproteinases (MMPs) is a hallmark of rheumatoid arthritis (RA) and osteoarthritis (OA). We have shown that MMP-9 activity in OA synovial fluid was preserved by the formation of a complex between the enzyme and neutrophil gelatinase-associated lipocalin (NGAL) but dissolution of the MMP-9/NGAL complex resulted in the auto-degradation of MMP-9 and loss of MMP-9 activity. Interleukin-6 (IL-6) and tumor necrosis factor-&#xoo3B1; (TNF-&#xoo3B1;) are 2 pro-inflammatory cytokines found in synovial fluid of RA and OA patients. In this study, human juvenile immortalized chondrocyte cell lines were employed to determine the extent to which recombinant human IL-6 (rhIL-6) and recombinant human TNF-&#xoo3B1; (rhTNF-&#xoo3B1;) increased MMP-9 production measured with an MMP-9 ELISA. We also determined if rhIL-6 blockade with Tocilizumab altered production of MMP-9 in response to rhIL-6. We used the pancreatic carcinoma cell line, PANC-1, which was previously shown to produce MMP-9 in response to phorbol myristate acetate (PMA), as the positive control for MMP-9 production. Thus, PMA (30.7 ng/ml) increased MMP-9 production after 24 hrs, from <100 pg/ml to >800 pg/ml. By comparison, after 24 hrs, rhTNF-&#xoo3B1; (20 ng/ml) increased chondrocyte MMP-9, from <50 pg/ml to 1200 pg/ml. In the presence of rhIL-6 (50 ng/ml), MMP-9 production increased from <50 pg/ml to 200 pg/ml. This was reduced by about 50% when Tocilizumab (200 ng/ml) was added together with rhIL-6. Of note, neither rhIL-6 nor rhTNF-&#xoo3B1; altered the production of MMP-9 by PANC-1 cells.
Vaccinogen, Inc., USA
Time : 09:25-09:50
Michael G. Hanna, Jr. received his PhD in experimental pathology and immunology from the University of Tennessee in 1964. He was on staff of the Oak Ridge National Laboratory, biology division from 1964-75. During this period he pioneered the early concepts of tumor immunology. He also served as a consultant with NASA for the lunar receiving laboratory during Apollo 11 and 12, for which his expertise in immunology was used in the testing of the lunar core powder for immunogenic or pathogenic materials. Dr. Hanna served during1975–83 as Director of the National Cancer Institute, Frederick Cancer Research Center (MD, USA). In this position he created a center of research excellence for the NCI and established the Biological Response Modifier Program which led in the development of resources for immunotherapy of cancer. rnrnHe was Chief Operating Officer during 1984–94 of Organon Teknika/Biotechnology Research Institute and Senior Vice President of Organon Teknika Corporation, a subsidiary of Akzo Nobel, The Netherlands. He developed and obtained approvals for TICE BCG for the treatment of carcinoma in situ (CIS) bladder cancer, which remains the standard of care for prophylaxis of recurrence of superficial bladder cancer and therapy of CIS. Subsequently, Dr. Hanna founded PerImmune Inc., for which he served as President and Chief Executive Officer before it merged with Intracel Corp. in1998. He continued to work for Intracel Resources as Chief Scientific Officer and Chairman.rnrnIn 2007, Dr. Hanna founded Vaccinogen Inc., where he served as Chairman and CEO. Currently, Dr. Hanna is Chairman Emeritus. The company is a pioneer in the field of cancer vaccines and is developing OncoVAX, an autologous vaccine designed to elicit a specific immune response against cancer cells. The Phase III vaccine is being investigated for treatment mainly of colon cancer, but also for melanoma and renal cell carcinoma. In addition to cancer therapy research and development, Dr. Hanna has been involved in Homeland Security. He served as Chairman of the Department of Commerce Biotechnology Advisory Committee (1984–9) and also participated in the Department of Defense Technical Working Group for Biotechnology (1988–9). PerImmune completed a Department of Defense contract to manufacture the current effective therapeutic for Botulinum toxin, an equine heptavalent anti-toxin.rnrnDr Hanna’s research resulted in over 225 publications in international peer-reviewed journals and book chapters, and he holds 10 patents related to immunotherapy. Dr Hanna has been the recipient of numerous honors and awards and has serves on many editorial boards.rn
While it has always been presumed that neoplasia is a consequence of somatic cell mutations, only in the last few years has the magnitude and diversity of these mutations been elucidated by modern DNA sequencing technology. Immunotherapy is the premier biological approach to targeted therapy. Target therapies require targets. In this case the targets are tumor specific or associated antigens, the proteins expressed from these somatic cell mutations. While the immunotherapeutic approach to eliminating cancer was launched with the assumption that cancer cells were homogeneous, the recent genomic understanding of tumor cells indicates that there is both inter- and intra-tumoral heterogeneity. This presentation will discuss the consequences of this new knowledge of tumor cell biology to the immunotherapeutic approach to treating cancer. What is more, this presentation will discuss the translational development of an active specific immunotherapeutic approach from preclinical to beneficial clinical benefit.
National Cancer Institute-Frederick, USA
Time : 09:50-10:15
Howard Young obtained his Ph.D. in microbiology at the University of Washington and carried out postdoctoral research at the NCI under Drs. Edward Scolnick and Wade Parks. He was a member of the Laboratory of Molecular Immunoregulation at NCI from 1983 to 1989 prior to joining the Laboratory of Experimental Immunology in 1989. He was President of the International Society for Interferon and Cytokine Research (2004-2005) and served as Chair of the Immunology Division of the American Society for Microbiology. He has also served as Chair of the NIH Cytokine Interest Group and Co-Chair of the NIH Immunology Interest Group. He is a two-time recipient of the NIH Director\'s Award for Mentoring (2000, 2006) and in 2006 he received the National Public Service Award. In 2007 he was named Deputy Chief of the Laboratory of Experimental Immunology.
Interferon-gamma (IFN-g) affects both the innate and adaptive immune response. We have created a 162 nt substitution of the AU-rich element (ARE) in the 3’UTR of the IFN-g gene, resulting in a stabilized IFN-g mRNA and chronic low levels of circulating IFN-g protein. The ARE-deleted (ARE-Del) mice develop a lupus-like disease characterized by the presence of autoantibodies and glomerulonephritis. IFN-g induced gene expression remains high at 3, 6 and 12 weeks of age indicating that there is no desensitization to the effects of this cytokine. Furthermore, the changes in gene expression contribute to an altered serum metabolome by 12 weeks of age. Greater percentages of B cells are found in the lymph nodes and thymus with a decrease observed in splenic B cells. Marginal zone B cells and macrophages are absent but can be restored by elimination of TLR7 or the Type 1 IFN receptor. Overall, we demonstrate that chronic low serum IFN-g levels (30-40 pg/ml) promotes the development of SLE-like disease and suggest that IFN-g gamma expression may contribute to disease in at least a subset of lupus patients.
University of Michigan Medical School, USA
Time : 10:15-10:40
I am Oliver, Associate Professor in Unit for Laboratory Animal Medicine (ULAM) and Department of Microbiology and Immunology. I am also an affiliated member of the Center for Computational Medicine and Biology (CCMB) and a member of the (Comprehensive Cancer Center) in the University of Michigan (UM) Medical School. Our laboratory research is focused on host-Brucella interaction and bioinformatics. I had my D.V.M. education at Jiangxi Agricultural University and my M.S. degree (Co-advisors: Professors Zhongzhi Zhang and Hanchun Yang) in Infectious Diseases and Veterinary Preventive Medicine at China Agricultural University in China. I obtained my professional assistant veterinarian license during my two-year employment at Beijing Xijiao Livestock and Poultry Company, Beijing, China. My training in Brucella research started in 1996 in Dr. Gerhardt Schurig’s immunology laboratory at the Virginia Polytechnic Institute and State University (Virginia Tech). I obtained my Ph.D. in Dr. Schurig's lab in 2000. I then worked in the same lab as a postdoc for half a year. I obtained my M.S. degree (research advisor: Dr. Pedro Mendes) in computer science in Virginia Tech with a focus on bioinformatics in May 2002. After graduation I worked as a senior research associate for three years in Dr. Bruno Sobral’s group at the Virginia Bioinformatics Institute (VBI). I joined UM in July 2005 as an assistant professor and became an associate professor in September 2011 (with tenure).
With the ever-increasing volume of publications in host-pathogen interactions, it is very challenging to integrate and analyze published big data and knowledge. Our studies have first identified a caspase-2-mediated proinflammatory cell death, which exists in macrophages and dendritic cells infected with a live attenuated vaccineBrucella strainRB51. This type of cell death is different from non-proinflammatory apoptosis or caspase-1-mediatedproinflammatorypyroptosis, and so we named the cell death "caspase-2-mediated pyroptosis". Interestingly, virulent Brucella inhibits such cell death in infected macrophages but not in dendritic cells. Our current confusions are how to understand more about the pathway and how to integrate this pathway with other cell death pathways modulated by variousinfections and vaccinations. To support knowledge integration and advanced data analysis, the presenter proposes an integrative One Network ('OneNet') Theory of Life, which treats the whole process of a life of an organism as a single integrative, complex, and dynamic network (called “OneNet”). Based on this theory, one host organism will utilize a single complex interaction network to respond to different pathogen infections or vaccinations. The OneNet interaction networks of one organism can be better represented and studied using biological ontologies. An ontology is a human- and computer-interpretable set of terms and relations that represent entities in a specific domain and how these terms relate to each other. Like the Periodic Table of Chemical Elements that represents the information of various chemical elements, ontologies can be used to systematically represent and analyze host responses to infections and vaccinations.