Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 3rd International Conference and Exhibition on Clinical & Cellular Immunology Baltimore, USA.

Day 1 :

OMICS International Immunology Summit-2014 International Conference Keynote Speaker Charles J Malemud photo
Biography:

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.

Abstract:

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.

Keynote Forum

Michael G. Hanna

Vaccinogen, Inc., USA

Keynote: The Provocative issue of tumor genomic heterogeneity in immunotherapy

Time : 09:25-09:50

OMICS International Immunology Summit-2014 International Conference Keynote Speaker Michael G. Hanna photo
Biography:

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

Abstract:

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.

Keynote Forum

Howard A. Young

National Cancer Institute-Frederick, USA

Keynote: Chronic interferon-gamma expression: Impact on the host

Time : 09:50-10:15

OMICS International Immunology Summit-2014 International Conference Keynote Speaker Howard A. Young photo
Biography:

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.

Abstract:

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.

Keynote Forum

Yongqun Oliver He

University of Michigan Medical School, USA

Keynote: How a host organism responds to various microbial infections and vaccinations?

Time : 10:15-10:40

OMICS International Immunology Summit-2014 International Conference Keynote Speaker Yongqun Oliver He photo
Biography:

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).

Abstract:

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.

Break:
Group Photo
 
Coffee Break 10:40-10:55 @ Foyer
  • Track 3: Inflammatory/Autoimmune Diseases
    Track 4: Cancer and Tumor Immunobiology
Location: Harbor Room
Speaker

Chair

Michael G. Hanna

Vaccinogen Inc., USA

Speaker

Co-Chair

Anil Shanker

Meharry Medical College, USA

Session Introduction

Howard A. Young

National Cancer Institute-Frederick, USA

Title:

Time : 10:55-11:15

Speaker
Biography:

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

Abstract:

Anil Shanker

Meharry Medical College, USA

Title: Cancer therapy by resuscitating immune surveillance

Time : 11:15-11:35

Speaker
Biography:

Anil Shanker is an Associate Professor in the Department of Biochemistry and Cancer Biology at Meharry Medical College. He is also a member of Vanderbilt-Ingram Comprehensive Cancer Center at Vanderbilt University. Dr. Shanker obtained his PhD from Banaras Hindu University in 1999. He performed his postdoctoral studies at the CNRS/INSERM Center of Immunology, Marseille, France and the National Cancer Institute, Frederick, Maryland. His pioneering work with solid tumor models demonstrated that activated CD8 T cells provided a necessary “help” to dormant NK cells in eliciting their antitumor function. His laboratory is currently focused on understanding mechanisms of functional cross-talk between T cells and NK cells in tumor models. He is also dissecting the mechanisms of immunomodulation by the proteasome inhibitor bortezomib and Notch ligand DLL1 in adoptive T cell/NK cell transfer settings in an effort to design novel combinatorial immune strategies in cancer patients. He has over 30 research publications to his credit in cancer and immunology journals.

Abstract:

Local tumor antigen-specific T cell-NK cell collaboration is indispensable for the elimination of tumor cells, including antigen-deficient tumor escape variants before metastasis. While mechanistic details are available for the innate instruction of the T cell responses, little is known for the adaptive control of NK cell activity. We observed in a mouse model of mastocytoma expressing a self tumor antigen P1A that effector CD8+ T cells provided a necessary “help” to dormant NK cells in eliciting their antitumor effector function. Bioluminescence imaging of mastocytoma tumors following adoptive transfer of P1A-specific T cells in RAG-/- and RAG-/-�γc-/- mice showed that NK cell anti-tumor activity requires cytolytic T cells, whereas T cells can function independent of NK cells. In 2D and 3D co-culture systems, we observed that PMA/ionomycin-stimulated CD8+ T cells form multiple contacts with naïve NK lymphocytes. Data show that NK cells interacting with activated CD8+ T cells show an up-regulation of CD25 and CD69 expression mediated by intercellular contacts, and activation of NKG2D receptors and Stat2, Stat6, Jak1, Jak3, Tyk2, and PTEN signaling molecules with a decrease in the phosphorylation of Stat1, PKB/Akt, SAPK/JNK, p38. On the other hand, interacting NK cells down-regulate CD25 molecule expression on CD8+ T cells and promote differentiation of central-memory CD44+CD62L+ T cells. CD8+ T cells display an elevation in the phosphorylation of Stat1 and down-regulation of Stat5 with stimulated PKB/Akt, Lck, mTOR, and p42/p44. Moreover, significant changes in the cytosolic and mitochondrial Ca2+, production of mitochondrial ROS, mitochondrial membrane potential, mitochondrial permeability transition pore, and synthesis of nitric oxide and non-protein thiols (mostly, reduced glutathion) were observed in a reciprocal T cell-NK cell interaction. These results highlight the importance of mitochondrial activity in the re-modeling of activation signaling and memory differentiation of interacting CD8 T cells and NK cells. These results will help refine cancer immunotherapeutic strategies.

Speaker
Biography:

Philip J Lucas received his PhD from The George Washington University, Washington, DC in 1991 in Immunology and Molecular Biology and completed his postdoctoral studies withthe Howard Hughes Medical institute at Washington University School of Medicine in St. Louis, MO with Dr. Dennis Loh. He is currently a Staff Scientist in the Experimental Immunology and Transplantation Branch, NCI, NIH where he studies the effects of stem cell transplantation on the thymus.

Abstract:

Thymic recovery can be a rate limiting process in full immunological recovery following chemotherapy. Emerging literature suggests that thymic insufficiency may have significant clinical consequences, exacerbating graft-versus-host disease and compromising the graft-versus-leukemia effect. Data have demonstrated that the thymus is damaged following current transplant preparative regimen, with a disproportionate depletion of UEA+ thymic epithelial cells (TEC). Very little is known about the effects of the individual components of such preparative agents. We have established an array of 25 murine genes expressed throughout the thymus, including UEA+ TEC, Ly51+ TEC and all thymocytes. Using quantitative PCR, we were able to use expression levels from this panel of genes to monitor the effects of chemotherapeutic agents on the thymus. To establish feasibility of this model, we first studied the effect of cyclophosphamide, a common agent in many chemotherapeutic regimens. Using a dose of 120 mg/kg x 2, we found significant changes (p<0.05) in 11 of 23 genes in the TEC populations (2 up and 9 down), as well as, 11 genes in the thymocyte population (11 down). Our data suggests that our current panel of thymic expression genes is capable of detecting changes after treatment with potential thymus altering agents.

Speaker
Biography:

Dr. Chien-Fu Hung is an associate professor of pathology and oncology and a professor of gynecology and obstetrics at the Johns Hopkins University School of Medicine. His research focuses on the prevention and treatment of cervical and ovarian cancers. His team is currently using an ascitogenic ovarian/peritoneal tumor model to investigate DNA vaccine strategies encoding ovarian tumor antigens identified by microarray and SAGE. Dr. Hung earned his Ph.D. in molecular biology from the University of Illinois. He completed a fellowship in pharmacology at the University of Pennsylvania and a fellowship in pathology at the Johns Hopkins University. He received a Young Investigator Award from the Alliance for Cancer Gene Therapy in 2004.

Abstract:

Selectively coating tumor cells with foreign antigenic peptide may render coated tumor susceptible to immune recognition and elimination, thereby bypassing immune tolerance. Here we create a therapeutic chimeric protein comprised of a tumor-homing module fused to a functional cargo domain containing foreign antigenic peptide. The tumor-homing module is comprised of mesothelin-specific single chain variable fragment that specifically binds to mesothelin, commonly overexpressed in ovarian tumors. The functional cargo domain is comprised of Fc (IgG2a) protein and MHC class I-restricted foreign CD8+ T cell epitope flanked by furin cleavage sites, which can be recognized by furin highly expressed in the tumor microenvironment. We show that our therapeutic protein specifically loaded antigenic epitope onto MHC class I of bound tumor cells, rendering them susceptible to antigen-specific CD8+ T cell-mediated killing for potent antitumor effects in vitro and in vivo. Our findings have important implications for bypassing immune tolerance to enhance cancer immunotherapy.

Speaker
Biography:

James Mansfield is a scientist with over 25 years of experience in spectral imaging,in-vivo spectroscopy and applied data analysis, directed towards finding of novel optical methods for the diagnosis and monitoring of medical conditions. He is currently the Director of Quantitative Pathology Applications at PerkinElmer where he is the senior application scientist for their multispectral and digital pathology product lines. He is an associate editor of the American Journal of Nuclear Medicine and Molecular Imaging, holds 6 patents, has over 50 publications and has served as an invited speaker, session chair and organizer at a variety of international conferences.

Abstract:

Successes with PD-L1 drugs and adoptive immunotherapy demonstrate the efficacy of leveraging the immune system to fight cancer. However, host-tumor interaction is complex and difficult to characterize with immunohistochemistry or flow cytometry. Visual assessment cannot easily determine the phenotype of immune cells in-situ and multimarker quantitation in FFPE tissue sections is difficult if not impossible with standard methods. Capturing spatial relationships of immune phenotypes in and around tumor would be advantageous, potentially forming the basis of assays to guide therapy and monitor response. To address this we present a multi-marker, computer-aided event-counting methodology for determining the phenotypes of immune and other cells in a range of tumor types using a multispectral imaging (MSI) automated tissue segmentation and cell counting approach. Arange of protocols on FFPE sectionswill be shown, including one for melanoma samples, with simultaneous labels for PD-L1, CD8, CD34, and FOXP3, and DAPI, and the other on follicular lymphoma, with labels for CD3, CD69, FOXP3 and hematoxylin. Results demonstrate reliable detection and phenotyping of lymphocytes in heterogeneous clinical samples, high signal-to-background and precise measurement of per-cell expression, and counts and distributions of phenotyped immune cells in both intra- and extra-tumoral compartments. We believe we have demonstrated a new capability for elucidating the intricacies of cancer immune response, for research and potentially for clinical use, with a workflow that is automated by computer and amenable to present practices where results are reviewed by pathologists to assure data quality.

Speaker
Biography:

I am currently the Head of Cellular Immunology Group at the Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute My research interest is in the role of the human immune response to tumor-associated antigens. We are working to define and develop immunodominant determinants and modifications of those determinants toward the optimal activation of human immune responses to tumor-associated antigens. Additionally, we are involved in studying mechanisms to enhance the potency of antigen-presenting cells for specific T cell activation. We are also developing immunologic methods and immunoassays to better define the efficacy of vaccine therapies for a range of human cancers.

Abstract:

Purpose:
The MUC1 tumor-associated antigen is overexpressed in the majority of human carcinomas and several hematologic malignancies. Much attention has been paid to the hypoglycosylated VNTR region of the N-terminus of MUC1 as a vaccine target, and recombinant viral vector vaccines are also being evaluated that express the entire MUC1 transgene. While previous studies have described MUC1 as a tumor-associated tissue differentiation antigen, numerous studies have now determined that the C-terminus of MUC1 (MUC1-C) is an oncoprotein, and its expression is an indication of poor prognosis in numerous tumor types.
Experimental Design:
We report here the identification of seven potential CD8+ cytotoxic T lymphocyte epitopes of MUC1: five in the C-terminus and two in the VNTR region, and have identified enhancer agonist peptides for each of these epitopes. These epitopes span HLA-A2 and A3 MHC class I alleles, which encompass two thirds of the population.
Results:
The agonist peptides, compared to the native peptides, more efficiently (a) generate T-cell lines from the peripheral blood mononuclear cells of cancer patients, (b) enhance the production of IFN-γ by peptide-activated human T cells, and (c) lyse human tumor cell targets in an MHC-restricted manner.
Conclusions:
The agonist epitopes described here can be incorporated in various vaccine platforms and for ex vivo generation of human T cells. These studies thus provide the rationale for the T-cell-mediated targeting of the oncogenic C-terminus of MUC1, which has been shown to be an important factor in both drug resistance and poor prognosis for numerous tumor types

Ahmed G. Hegazi

president of the Egyptian Environmental Society
National Research Center, Egypt

Title: Influence of honey in mice bearing Ehrlich carcinoma on immune status

Time : 12:55-13:15

Speaker
Biography:

• Awarded the Excellent Medal of the First Class, 1995 • Received the Senior Scientist Prize of National Research Center, 1996 • Received the National Scientific Prize In Biological Sciences, 1990 • Received the Scientific Prize of The National Research Center, 1989 • Won The Second Best Research Paper award From International Congress of propolis, Argentina, 2000 • Mean speaker in 10th Academic conference, , 2006, Japan • From Wikipedia, Awarded 2 Bronze medals from “The International Innovation Fair of the Middle East”, , 2007, Kuwait. Prof. of Microbiology & Immunology ,National Research Center National Research Center, Dept. Parasitology, 1997-2000, Chair • Faculty of Medicine, Zagazig University, 1981-1997, Par-time Prof. and Supervisor on Immunology Section • National Research Center, 1990- up till now, Prof. of Microbiology & Immunology • African Federation of Apiculture Associations (AFAA), 2001- up till now, • Standing Commission on Apitherapy (APIMONDIA), 1999 - up till now, Member • Standing Scientific Committee, National Research Center, 1998 –up till now, • First, Second and Third Annual Conference of the Egyptian Association of Immunologists 1993, 1994 and 1996, Secretary General • Egyptian Journal of Immunology, 1995, Editorial Board • The Egyptian Association of Immunologists, 1992 –1997, Secretary General • Referee in 37 International Journals Patents: 4 Patents Educational Activities • Organized training courses on Immunology, National Research Center, 1987-2002 • Conducted training courses on Immunology, Faculty of Medicine, Zagazig University, 1981-1997 • Supervised the Immunology lab, Faculty of Medicine, Zagazig University, 1981-1997 The publications: • 193 articles in national and international scientific journals • 6 books in English language • 7books in Arabic language

Abstract:

Antitumor effect of coriander honey (500 mg/kg) was investigated in mature mice bearing Ehrlich carcinoma with special reference to immune status. The coriander honey showed decrease in tumor volume, packed cell volume and viable cell count, and increased the non-viable cell count and mean survival time thereby increasing life span of EAC tumor bearing mice. The results of the effect of honey on immunological status in the mice bearing Ehrlich carcinoma observed that the immunoglobulin level (M, G and A) was raised in all groups if compared with the control group all over the experimental period. The rises were differed according to the treatment. It was clear that the phagocytic activity in mice bearing carcinoma was reduced if compared with the control group. The group treated with honey showed an increase in phagocytic activity. Also the groups treated with honey after inoculation with Ehrlich carcinoma (Ascites and Solid) revealed an increase in the phagocytic activity than carcinoma only and control group. There was reduction in the stimulation indices of stimulation indices of lymphocyte transformation of mice bearing Ehrlich carcinoma. Delayed hypersensitivity skin test revealed that the Ehrlich carcinoma reduced the reaction especially after 72 hours post inoculation with bovine serum albumin. The reaction in the Ehrlich carcinoma and subsequently treated with honey showed a rise in thickness ranging from 0.62 mm skin thickness in case of Ascites where the solid state was more higher 0.73 mm thickness. It could be concluded that, the coriander honey exhibited antitumor effect by increases cell mediated and immunoglobulin levels, in EAC bearing mice.

Break: Lunch Break 13:15-14:00 @ Eden’s Landing Restaurent
Speaker
Biography:

NarayananParameswaran obtained his Veterinary Medicine degree from Madras Veterinary College, India and a PhD from Michigan State University, East Lansing. After a post-doctoral fellowship at Thomas Jefferson University, he started his independent career at Michigan State University in 2006. He has published more than 45 peer-reviewed manuscripts in reputed journals. He currently serves as editorial board member for Genes and Immunity and is also an appointed member of the Innate Immunity and Inflammation study section at the National Institutes of Health. In addition he has served on several other grant review panels including the American Heart Association.

Abstract:

β-arrestins (β-arrestin-1 and 2) are scaffolding proteinsoriginally identified as critical regulators of G-protein coupled receptor (GPCR) desensitization. More recent studies indicate that the functions of β-arrestins are much broader and include a wide variety of cell signaling functions including their role in biased signaling from GPCRs. Studies from our lab and others demonstrate a critical role for β-arrestins in non-GPCR signaling including receptors involved in inflammation, such as TLRs.In previous studies we found that β-arrestin1 (β-arr1) is a critical mediator of endotoxemia in mouse model. Consistent with that, we also found that the β-arr1 deficient mice are protected from intestinal inflammation. Accordingly, β-arr1 deficient mice also exhibited significantly low levels of IL-6 compared to wild type mice during colitis. By generating bone marrow chimeras, we further found that deficiency of β-arr1 in the hematopoietic compartment is sufficient to prevent colitis-induced weight loss. Surprisingly however, we found that β-arr1 deficient mice are strikingly more susceptible to polymicrobial sepsis induced by cecal ligation and puncture. This opposing phenotype also correlated with enhanced levels of IL-6 in the β-arr1 knockout mice. Intriguingly, we further found that the negative regulatory role of β-arr1 in the polymicrobial sepsis model is attributable to regulation of IL-6 by β-arr1 in the non-hematopoietic cells. Together our results suggest that β-arr1 in different cellular compartments have selective and unique roles depending on the instigating stimuli in terms of inflammatory disease.

Speaker
Biography:

Loui Madakamutil has completed his PhD from Mumbai University and postdoctoral studies from La Jolla Institute for Allergy and Immunology, San Diego. He is the director and site head of Immunology Drug Discovery Unit Takeda California. He is an immunologist with more than 14 years of expertise in all aspects of small molecule and biological drug discovery process from hit to lead and first in human studies.

Abstract:

Takeda California utilized a structure based drug discovery approach to identify novel small molecule inhibitor of BTK. This talk will highlight the potential for the BTK small molecule inhibitor to control B cell and Fc receptor mediated immune pathology. Compound 9 the lead candidate was evaluated in vitro for its effect on B cell receptor (BCR) and Fc receptor mediated cellular function. Further compound 9 was tested for in vivo therapeutic effects in the rodent models of CIA and in the anti-GBM induced kidney damage model. These studies revealed that BTK is a viable target for identifying novel approaches to treat several autoimmune diseases that are mediated with B cell and Fc receptor diseases including rheumatoid arthritis and immune complex mediated kidney damage.

Gregory Lee

UBC Center for Reproductive Health, Canada

Title: Potential roles of cancerous immunoglobulins in cancer immunology

Time : 14:40-15:00

Speaker
Biography:

Gregory Lee upon completion of his Ph.D. degree in Biophysical Chemistry at California Institute of Technology in 1972 joined UCSD as a NIH Postdoctoral Fellow to carry out pioneer work on general ligand affinity chromatography. In 1976, he studied enzymology and biochemical genetics at the National Institute of Health and in 1981, he was appointed as a professor and director of the Andrology Laboratory at the University of British Columbia. During the last two decades, he has created numerous monoclonal antibodies for diagnostic and therapeutic applications in human health care, including RP215 and GHR106 for potential use as anti-cancer drugs. He has been serving as an editorial board member for Journal of Cancer Science and Therapy, American Journal of Cancer Review, American Journal of Cancer Science, and Journal of Biochemistry and Physiology.

Abstract:

Expressions of immunoglobulins essential for growth/proliferation of cancer cells have been known for decades. However, the detailed mechanisms of action and their roles in the immunity of cancer cells are not fully understood. RP215 is a monoclonal antibody generated against cancer cell extract and was shown to react mainly with a carbohydrate-associated epitope in the heavy chains of immunoglobulins on the surface of all human cancer cells, but not in normal immune cells. Through years of studies with RP215 as the unique probe, it is now established that RP215 and goat anti-human IgG act biosimilarly on cultured cancer cells, including induced apoptosis, complement-dependent cytotoxicity as well as gene regulations. Both were shown to regulate genes involved in the growth/proliferation as well as the innate immunity of cancer cells with high correlations. Previous studies also indicated that cancerous immunoglobulins are expressed with molecular mechanisms completely different from those of normal immune cells in our human body. Therefore, the expressed cancerous immunoglobulins maybe playing key roles to neutralize circulating “antigen” within the body for immune protection of cancer cells. Both normal and cancer immune systems can operate independently in our body. We believe that a better understanding about the underline mechanisms of cancerous immunoglobulins may lead to a more realistic strategy for cancer immunotherapy in humans.

Speaker
Biography:

Joanna Trojanek has completed the PhD of Biochemistry from Institute of Biochemistry and Biophysics Polish Academy of Sciences in 1991. She was postdoctoral fellow at Center for Neurovirology and Cancer Biology, Department of Biology, Temple University, Philadelphia, USA for three years and afterwards at Department of Translational Pulmonology , University Children Hospital, Heidelberg, Germany for next three years. From 2010 she is Research Associate in Microbiology and Clinical Immunology Department at The Children’s Memorial Health Institute. She has published about 18 papers in peer-reviewed journals. The main research areas are reflected to gene and protein expression profiles involved in pathogenesis and development of primary hypertension and other metabolic syndromes in children’s leukocytes.

Abstract:

Primary hypertension (PH), non-alcoholic fatty liver disease (NAFLD) and obesity are all related to a systemic low-grade inflammation, vascular remodeling, visceral obesity, insulin resistance, and dyslipidemia. However, NAFLD children rarely develop PH. The aim of this study was to assess peripheral blood leukocyte (PBLs) gene expression profiles of mediators involved in extracellular matrix degradation, vascular remodeling and inflammation in the normal weight PH, obese PH, NAFLD and obese, normotensive, non-NAFLD, healthy children, aged 9-16 yrs, compared to healthy, age-matched, normal weight (only for obese PH – obese healthy) control group. This approach makes possible to find out which of tested factors is related to PH or NAFLD regardless of obesity. Total leukocyte mRNA expression levels were measured by quantitative RT-PCR (real-time reverse transcriptase-polymerase chain reaction). Relative target gene expression level, compared to control group was normalized by expression of the reference gene – G3DPH. We tested the expression of a) matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), including MMP-9, MMP-2, MMP12, MMP14, and TIMP-1, TIMP-2, respectively, and b) mediators: insulin like growth factor -1 receptor (IGF-1R); transforming growth factor beta (TGF); and interleukin-6 (IL-6). The normal weight PH patients (pts) expressed high levels of MMP-14, increased MMP-2, slightly elevated MMP-9, TIMP-1,2, with only moderately increased IGF-1R, TGF-beta and IL-6 compared to healthy, normal weight control. The obese PH pts had 2-fold higher expression of MMP-9, MMP-2, and IL-6, slightly increased MMP-12, 14, and decline in TIMP-1/2, TGF-beta, and IGF-1R, as compared to normal weight PH pts. The NAFLD pts were characterized by increased of MMP-9 (equal to that of normal weight PH pts) and rather low expression of other mediators studied, except for high TGF-beta gene expression levels. The obese, normotensive, non-NAFLD pts had increased MMP-9, MMP-12, but very low MMP-2 expression as compared to normal weight controls, with no significant changes in the expression of other mediators studied.

Conclusions

1. Increase in leukocyte MMP-2, MMP-14 and IL-6 gene expression seems to be more related to PH than to obesity. It possibly predisposes to increase in vascular remodeling and elevation of arterial stiffness due to vessel wall elastin degradation and immature collagen deposition.
2. In contrast, MMP-9 and MMP-12 gene expression levels are related rather to obesity but less to PH.
3. NAFLD was related to selective increase in leukocyte TGF-beta gene, more balanced expression of MMPs and TIMPs, with low IL-6 and IGF-1R gene expression levels. It may reflect less vigorous arterial wall remodeling and vascular activation

Paloma Manea

Grigore T. Popa University of Medicine and Pharmacy, Romania

Title: Comparison between C reactive protein and microalbuminuria levels for the prognosis of renovascular hypertension

Time : 15:20-15:40

Speaker
Biography:

Paloma Manea MD, Ph D, FACCP is a specialist in Cardiology and Internal Medicine, competence in echocardiography, lecturer at ’’Grigore T.Popa’’ University of Medicine and Pharmacy, Iasi, Romania. In 2013, she discovered the 6th case (there are only 5 communicated cases, worldwide) of spontaneous closure of an interventricular septal defect after a myocardial infarction. She has published and communicated 80 scientific works. The main research areas are related to angiotensin-renin-aldosterone system, skin cancer, correlations between dentistry and medical diseases, geriatric pathology.

Abstract:

76 elderly patients with renal artery stenosis were enrolled in our 20 months study. The assesment of the patients included the following: a complete clinical examination, electrocardiogram, echocardiogram, renal artery sonography, abdominal computed tomography, laboratory findings. We’ve compared two important parameters in order to establish their role among patients’ prognosis: C reactive protein and microalbuminuria levels. Renal dysfunction (worsening of the serum creatinine clearance) was strongly correlated with high levels of C reactive protein and it had a weaker association with microalbuminuria. 92% patients with high levels of C reactive protein had dental plaque and correct removal of the plaque lead to the lowering of C reactive protein levels; this atitude (scaling) was followed by an improvement of serum creatinine clearance or at least a stable value. These observations had an impact regarding the holistic approach of renovascular hypertension and delimited new targets for a proper therapy of these patients.

Maria Celia Jamur

University of Sao Paulo, Brazil

Title: The role of mast cell proteases in tumor angiogenesis

Time : 15:40-16:00

Speaker
Biography:

Maria Celia Jamurreceived her Ph.D. in Cell Biology in 1986 from the Ribeirao Preto Medical School. She was a post-doctoral fellow at the National Institutes of Health, Bethesda, MD. and was a professor in the Department of Cell Biology at the Federal University of Parana, Curitiba, Brazil. Currently, she is a Professor in the Department of Cell and Molecular Biology and Pathogenic Bioagents at Ribeirao Preto Medical School. She has authored more than 75 publications and is serving as an editorial board member for several Journals.

Abstract:

Tumors are surrounded by infiltrating inflammatory cells including mast cells. However, the function of mast cells in neovascularization and tumor progression remains obscure. Initially, the expression of mouse mast cell proteases (mMCP)-4, mMCP-5, mMCP-6, mMCP-7, and carboxypeptidase Awere analyzedduring progressionof chemically induced tumors in BALB/c mice. With the exception of mMCP-4,expression of these mast cell proteases increased with tumor progression. Additionally, the number of new blood vessels increased significantly in the early stage of tumor formation, while in the later stages an enlargement of existing blood vessels occurred (PLoS ONE,2012, 7:e40790). In order to understand the role ofmast celltryptasesinangiogenesis, SVEC4-10endothelial cells were cultured on Geltrex® with recombinant mMCP-6 or 7and tube formation was analyzed.The capacity of these tryptasesto induceproduction of pro and anti-angiogenic cytokines/proteinswas also investigated.rmMCP-6 and 7 were able to accelerate tube formation in SVEC4-10 cells. Co-cultivation of SVEC4-10 with P815 cells(mouse mastocytoma) also enhanced the process of tube formation. In the presence of these proteases,as observed by SEM, the SVEC4-10 cells penetratedinto the gel. However, incubation with the proteases did not alter the expressionor activityof metalloproteases.Furthermore, rmMCP-6 and rmMCP-7 are able to induce the differential expression of pro- and anti-angiogenic factorsin SVEC4-10 cells.Therefore, both rmMCP-6 and rmMCP-7 can modulate angiogenesis, butrmMCP-7 is moreefficient ininducingtube formationand in the production of angiogenic factors.

Break: Coffee Break 16:00-16:15 @ Foyer
Biography:

Jean-François Fonteneau received the PhD degree from Nantes University, France, in 1999. During his thesis training, he studied CD8+ T lymphocytes response against melanoma in the INSERM Laboratory of Pr Francine Jotereau, Nantes, France. He then joined Dr Nina Bhardwaj’s group in Dr Ralph Steinman Laboratory as a Postdoctoral Fellow at Rockefeller University, New York, USA, from 1999 to 2003, where he studied dendritic cells (DC) biology, notably cross-presentation of viral and tumor antigens and interactions between virus/myeloid DC/plasmacytoid DC. In 2003, he returned to Pr Francine Jotereau Laboratory, INSERM U892, Nantes to identify new melanoma epitopes recognized by patient’s CD8+ and CD4+ T cells. In 2009, he joined Dr Marc Gregoire's Laboratory, INSERM U892, Nantes, to study attenuated measles virus as an oncolytic virus for antitumor virotherapy of pleural mesothelioma to induce immunogenic cell death of tumor cells.

Abstract:

Antitumor virotherapy consists in the use of oncolytic viruses able to infect and kill tumor cells without or with limited infection of healthy cells. Antitumor virotherapy is also able to induce or reinforce the antitumor immune response. Our group studies the Schwarz attenuated strain of measles virus (MV) for its oncolytic properties against various cancers, notably pleural mesothelioma. MV enters cells by the CD46 molecule that is often over expressed by numerous types of tumor cells. Recently, we studied how MV or MV-infected tumor cells can influence the antitumor immune response by studying their effects on myeloid and plasmacytoid dendritic cells (mDC and pDC) that are specialized in T cell response induction. We found that MV-infected tumor cells induced maturation of both types of DC, whereas tumor cells killed by UV-irradiation were not able to induce maturation. Then, we found that this maturation was mainly due to danger signals released by infected tumor cells for the activation of mDC and to MV ssRNA for the activation of pDC via TLR7. pDC maturation was accompanied by a strong production of IFN-α. In addition, we observed that MV-infected and UV-irradiated tumor cells were efficiently phagocytosed by mDC and pDC. Interestingly, we observed cross-presentation of the tumor antigen, NYESO-1, to a specific CD8+ T-cell clone only when mDC and pDC were cocultured with MV-infected tumor cells. Altogether, our results showed that the use of MV as an oncolytic virus induces immunogenic tumor cell death, allowing cross-presentation of tumor antigens by mDC and pDC. This phenomenon suggests that MV based antitumor virotherapy may strengthen the anti-tumor immune response by recruitment of DC.

Speaker
Biography:

Ljudmila Stojanovich received her PhD in Medicine, with the thesis “Neuropsychiatric manifestations in patients with Systemic Lupus Erythematosus” in 1999. She is the scientific director in the Bezhanijska Kosa, University Medical Center of Belgrade University, where she is currently a Research Professor. Her research focuses on Systemic Lupus Erythematosus, Antiphospholipid Syndrome, and Vaccination in patients with Autoimmune Rheumatic diseases. She is an author of three monographs and of about 250 articles on various aspects of Rheumatic disorders, published in international and domestic journals and in conference proceedings. She is in Editorial Boards /Reviewer in the “Current Contensts” or “Science citation index”, like LUPUS, Cellular and Molecular Neurobiology, The Journal of Vaccine, The Journal of Rheumatology, Allergologia et Immunopathologia and others. She is a member of number International Project, like of “the European Forum on Antiphospholipid Antibodies”, “Multicentre Studies Antiphospholipid Antibodies, Infections and Autoimmune Diseases”. She is a mentor/ Supervisor of a numbers of post-doc students.

Abstract:

Introduction:
Antiphospholipid syndrome (APS) patients suffer from various clinical manifestations with the presence of antiphospholipid antibodies (aPL). APS may manifest itself as a primary disease (PAPS) or as a secondary disease (SAPS), most commonly in the context of Systemic Lupus Erythemathosus (SLE)
Patients and methods:
We analyzed 488 patients: 346 PAPS (70.9%) (77.7% female and 22.3% male) average age 44.1±13.0 years and 142 patients with secondary APS (SLE) patients (29.1%) (90.8% female and 9.2% male) average age 47.2±14.8 years. aPL analysis included analysis of aCL (IgG/IgM), ß2GPI (IgG/IgM) and LA. aPL analysis included analysis of aCL (IgG/IgM), ß2GPI (IgG/IgM) and LA. In all patients data considering cardiac, vascular, pulmonary, neurological, skin and hematological disorders were collected.
Results:
There was 30.8% aCL-IgG, 49.7% aCL-IgM, 31.4% β2GPI IgG, 40.4% β2GPI IgM and 54.0% LA positive PAPS patients. Among SAPS patients 57.9% were aCL-IgG, 61.4% aCL-IgM, 40.7% β2GPI IgG, 45.0% β2GPI IgM and 51.1% LA positive. We observed 56.3% with neurological, 23.0% patients with skin, 27.3% with cardiac, 20.8% with hematological and 15.2% with pulmonary disorders. 54.3% of patients had peripheral vascular thrombosis (arterial, venous or both) in PAPS and 70.4% SAPS patients with skin, 77.3% with neurological, 40.8% with cardiac, 64.8% with hematological and 12.0% with pulmonary disorders. 57.9% of SAPS patients had peripheral vascular thrombosis. Between SAPS and PAPS patients we observed highly statisticaly significant difference considering neurological (p=0.0001), cardiac (p=0.002), skin (p=0.0001) and hematological manifestations (p=0.0001) in favour of patients with SAPS.
Conclusion:
Patients with SAPS suffer more often from various clinical features comparing to patients PAPS. Additional autoimmune burden in those patients presented through aPL presence besides actual autoimmune disease pannel, could be an explanation

Speaker
Biography:

Lisa M. Minter received her PhD and post-doctoral training at the University of Massachusetts/Amherst, and is now an Assistant Professor in the Dept. of Veterinary & Animal Sciences at UMass/Amherst. She has publications in several high-impact journals including Nature Immunology, Nature Reviews Immunology, Journal of Experimental Medicine, EMBO, and Blood. She has served as an ad hoc reviewer for Blood, Cellular and Molecular Immunology, Future Medicine and the American Journal of Pathology. Her research interests focus on Notch signaling in peripheral T cells and its contribution to the pathology of autoimmune bone marrow failure.

Abstract:

The objective of this study is to deliver anti-pPKCθ (T538) into T cells (hPBMCs) by using cell penetrating peptide mimics (CPPMs) to neutralize PKCθ activity both in vitro and in vivo, with the eventual goal of treating aplastic anemia (AA). AA is an immune-mediated bone marrow failure disease caused by T helper type 1 (Th1) autoimmune responses, which destroy blood cell progenitors. It was previously reported that protein kinase C theta (PKCθ), expressed specifically in T cells, plays an important role in T cell signaling by mediating Th1 differentiation. Mice treated with Rottlerin, a pharmacological inhibitor of PKCθ, were rescued from the disease when PKCθ phosphorylation was inhibited. Furthermore, humanized antibodies are increasingly gaining attention as therapies. The delivery of antibodies could be achieved via cell penetrating peptides (CPPs), which are able to internalize cargo into cells. Here, we designed, synthesized and characterized CPPMs to increase delivery efficiency of an antibody against phosphorylated PKCθ (T538), which subsequently interfered with the function of the kinase. We designed an in vitro delivery method for the CPPM/anti-pPKCθ complex then assessed T cell activation and AA disease marker expression. Also, we generated an in vivo humanized mouse model of AA and tested the complex for delivery and effect on survival of these mice. Altogether the results reveal that PKCθ may be an optimal target for bone marrow failure treatment and intracellular antibody delivery may represent a novel approach for AA treatment

Speaker
Biography:

Nancy J Bigley received the BS degree in bacteriology from Penn State University in 1953 and the PhD from The Ohio State University in 1957 and has taught immunology and microbial pathogenesis at The Ohio State University, Chicago Medical School and Wright State University. She has published more than fifty papers in the field and authored two editions of a textbook in immunology. Her areas of research involve viral and cellular immunity and more recently innate immunity at the cellular level.

Abstract:

Herpes simplex virus type 1 (HSV-1) infection was examined on murine J774A.1 and RAW 264.7 macrophage cell lines unpolarized (M0) or polarized by IFN-γ and or cytokines to either an M1 (pro inflammatory) or M2 (immunomodulatory and tissue remodeling) phenotype. Dengue virus2 (DENV2) infection of RAW264.7 cells was also investigated. Morphology, cell viability, expression of cell surface markers, expression ratios of suppressor of cytokine signaling molecules SOCS1/ SOCS3, and capacity to replicate HSV-1 were determined. Morphological differences were abrogated by virus infection. Infection with either virus diminished expression of CD14 and CD86 in M1 populations, cells which exhibited significant decreases (p<0.001) in cell viability at 24 hours post infection. Western blotting suggested that SOCS1/SOCS3 expression ratios differed between uninfected and HSV-1-infected RAW264. 7 M1 cells, while ratios in the uninfected cells and the DENV2-infected M1 cells remained similar. Flow cytometry demonstrated that this ratio between uninfected M1 cells and HSV-1-infected M1 phenotypes fell from 6:1 to 1:1 in M1 phenotypes of J774A.1 cells. SOCS3 expression increased7-fold in the M1 infected J774A.1 cells compared to uninfected M1 cells. Three- to four-fold decreases in HSV-1 yield occurred by 24 hours after infection in the M1 subpopulations. This decrease may reflect the anti-inflammatory effect of the relative increases in S0CS3 expression in these cells and/or the decreased survival of M1 cells after virus infection. Increases in SOCS3 expression by theHSV-1-infected M1 populations suggest a shift in the cell’s ability to respond to virus, a change not seen in DENV2 infection.

Speaker
Biography:

Myron R. Szewczuk received his Ph.D. (Biology and Immunochemistry) from the University of Windsor, Windsor Ontario in 1974 and completed his postdoctoral studies in Cellular Immunology under Dr. Gregory W.Siskind at Cornell University Medical College, New York City, in 1978. From 1978-81, Dr. Szewczuk was an Assistant Professor of Pathology at McMaster University, Hamilton, Ontario. In 1981, he joined the Dept. of Microbiology & Immunology (now Biomedical and Molecular Sciences) as an Associate Professor of Immunology at Queen’s University, Kingston, Ontario. In 1986, he received tenure and became full Professor of Immunology and Associate Professor of Medicine. He is presently a full time faculty member at Queen’s University with an active teaching and research program in immunology and cancer. He has published over 100 papers, chapters and reviews primarily in the field of immunology and cancer.

Abstract:

Snail, a transcriptional factor and repressor of E-cadherin is well known for its role in cellular invasion. It can regulate epithelial to mesenchymal transition (EMT) during embryonic development and in epithelial cells. Snail also mediates tumor progression and metastases. Silencing of Snail and its associate member Slug in human A2780 ovarian epithelial carcinoma cell line was investigated to identify its role in tumor neovascularization. Live cell sialidase, WST-1 and immunohistochemistry assays were used to evaluate sialidase activity, cell survival and the expression levels of tumor E-, N- and VE-cadherins, and host endothelial CD31+(PECAM-1) cells in archived paraffin-embedded ovarian A2780, A2780 Snail shRNA GIPZ lentiviral knockdown (KD) and A2780 SlugKD tumors grown in RAGxCγ double mutant mice. Oseltamivir phosphate (OP), anti-Neu1 antibodies and MMP-9 specific inhibitor blocked Neu1 activity associated with epidermal growth factor (EGF) stimulated A2780 ovarian epithelial carcinoma cells. Snail and Slug KD A2780 cells abrogated the Neu1 activity following EGF stimulation of the cells compared to A2780 cells. OP treatment of A2780 and cisplatin-resistant A2780cis cells reproducibly and dose-dependently abated the cell viability with a LD50 of 7 and 4 μM, respectively. Heterotopic xenografts of A2780 ovarian tumors developed abnormally robust and bloody tumor vascularization in RAGxCγ double mutant mice. Preclinical in vivo anti-tumor activity of OP monotherapy at 50 mg/kg daily intraperitoneally did not significantly impede A2780 tumor growth rate in a time-to-progression but did cause a significant reduction of lung metastases compared with the untreated and OP 30 mg/kg cohorts. A2780 Snail KD cells, but not the Slug KD member completely abrogated the tumor vascularization, growth and spread to the lungs in these mice. A2780 and A2780 Slug KD xenograft tumors expressed high levels of human N- and VE-cadherins, and host CD31+ endothelial cells, while one A2780 Snail KD tumor expressed higher levels of E-cadherin and host CD31+ cells. OP 50mg/kg cohort tumors had reduced numbers of host CD31+ cells compared to those from the untreated control and OP 30mg/kg cohorts. These findings uncover a novel organizational signaling platform connecting the Snail-MMP-9 signaling axis in amplifying the Neu1 sialidase and MMP-9 cross-talk in regulating EGF receptors, tumor neovascularization, growth and invasiveness.

Speaker
Biography:

Abdel-Azeem El-Mazary has completed his M.B.B.CH at the age of 24 years and M.D degree at the age of 34 years from Minia University, Egypt. Postdoctoral workshops and training courses in Pediatrics in both of Cairo and Mansoura Universities, Egypt. He is the director of Neonatology Unit Clinic of Minia University Hospital. He is working as Associate Professor in Pediatrics, Pediatric Departement, Minia University. He has published more than 16 papers in reputed journals and has been serving as an editorial board member of (Science Research Journal) and as a reviewer in (European Journal of Clinical Nutrition) .

Abstract:

Bezoars are masses formed by the accumulation of intra luminal non digestible substances that can lead to obstruction of the stomach and the small intestine. The anatomical changes in the gastrointestinal tract are known to cause bezoar formation. The so-called Rapunzel syndrome is the extension of the bezoars down to the duodenum and the jejunum, which is a rare condition. This may occur in subjects with mental retardation and/or psychiatric disorders. We present a 7-year-old girl with primary biliary cirrhosis who was admitted to our department with hematemesis, loss of weight and fatigue complaints along the last 6 months, in whom a giant trichobezoar was identified through endoscopy which completely filled the stomach and duodenum causing partial obstruction and needed surgical interference for removal and psychiatric therapy. We believe that -after MEDLINE search along the last 10 years- this case is the first Egyptian case report of this kind in the literature.
conclusion:
Trichobezoars should be considered as a differential diagnosis in children complaining of recurrent abdominal pain with epigastric mass and progressive loss of weight.Diagnosis can be easily made with radiological interventions and endoscopy. As a case report we present a 7-year-old Egyptian girl with primary biliary cirrhosis and Rapunzel syndrome at very young age.
Keywords: Rapunzel, trichobezoar, biliary, cirrhosis, female, Egyptian.

Break: Panel Discussion 18:15-18:30

18:30-19:30 Cocktails sponsored by Journal of Clinical & Cellular Immunology @ Foyer
Billie Holiday
  • Track 5: Vaccines
    Track 6: Immunotherapy
Location: Billie Holiday
Speaker

Chair

Charles J Malemud

Case Western Reserve University School of Medicine, USA

Speaker

Co-Chair

Yongqun Oliver He

University of Michigan Medical School, USA

Session Introduction

Ahmad G. Hegazi

National Research Center, Egypt

Title: Novel therapeutic modality of apitherapy for controlling of multiple sclerosis

Time : 10:55-11:15

Speaker
Biography:

• Awarded the Excellent Medal of the First Class, 1995 • Received the Senior Scientist Prize of National Research Center, 1996 • Received the National Scientific Prize In Biological Sciences, 1990 • Received the Scientific Prize of The National Research Center, 1989 • Won The Second Best Research Paper award From International Congress of propolis, Argentina, 2000 • Mean speaker in 10th Academic conference, , 2006, Japan • From Wikipedia, Awarded 2 Bronze medals from “The International Innovation Fair of the Middle East”, , 2007, Kuwait. Prof. of Microbiology & Immunology ,National Research Center National Research Center, Dept. Parasitology, 1997-2000, Chair • Faculty of Medicine, Zagazig University, 1981-1997, Par-time Prof. and Supervisor on Immunology Section • National Research Center, 1990- up till now, Prof. of Microbiology & Immunology • African Federation of Apiculture Associations (AFAA), 2001- up till now, • Standing Commission on Apitherapy (APIMONDIA), 1999 - up till now, Member • Standing Scientific Committee, National Research Center, 1998 –up till now, • First, Second and Third Annual Conference of the Egyptian Association of Immunologists 1993, 1994 and 1996, Secretary General • Egyptian Journal of Immunology, 1995, Editorial Board • The Egyptian Association of Immunologists, 1992 –1997, Secretary General • Referee in 37 International Journals Patents: 4 Patents Educational Activities • Organized training courses on Immunology, National Research Center, 1987-2002 • Conducted training courses on Immunology, Faculty of Medicine, Zagazig University, 1981-1997 • Supervised the Immunology lab, Faculty of Medicine, Zagazig University, 1981-1997 The publications: • 193 articles in national and international scientific journals • 6 books in English language • 7books in Arabic language

Abstract:


Objective:
Study the effect of bee sting therapy (Apitherapy) in treatment of Multiple Sclerosis.
Methods:
This study was carried on fifty patients known to be with MS, twelve males and thirty eight females, their ages ranged between 26-71 years, with a mean of 38.7 ± 4.8. 2. All cases were subjected to complete clinical and neurological history and examination to confirm the diagnosis. There were 32 cases with quadriparesis, (8 males and 24female) and 18 cases with paraparesis (4 males and 14 females). All cases were under their regular treatment either by corticosteroids, or interferon. These cases were divided into two main groups, each group consists of 25 cases (6 males and 19 females), Group I received honey, pollen, royal jelly and propolis and were treated with apiacupuncture 3 times weekly, for 12 months, started gradually by one sting then gradually increase up to 25 stings per session, in addition to their medical treatment, while group II remains on their ordinary medical treatment only. Apiacupuncture done by bee stings for regulating the immune system in the following points Du 13, 14, Li 11, S6, S9, points for MS Pat Wagner points for cervical area and lumber area and vision points GB2 and Li3. All patients were instructed to receive 2000-3000 mg Vitamin C, 15 mg Vit. B1, 3 mg Vit. B2, 2mg Vit. B6, 5 mg Vit. B12, 25 mg Folic acid, 3 mg Calcium pantothenate, 15mg Nicotinamide, 20 mg L- Arginine, 20 mg L- Lysine and 3 mcg Biotin / day.
Results:
Results revealed that 4 patients out of 9 (44.4% of paraparesis cases), showed some improvement regarding their defects in gait, bowel control, constipation and urination, while 12 cases out of 16 cases (75% of quadriparesis cases), showed some mild improvement in their movement in bed, and better improvement in bed sores, sensation, and better motor power, only two cases of them (12.5%) were able to stand for few minutes with support.
Conclusion:
Although Apitherapy is not a curable therapy in MS, but it can be used to minimize the clinical symptoms of MS, and can be included among programs of MS therapy.

Ruo-Pan Huang

Ray Biotech, Inc. - The Protein Array Pioneer Company, USA

Title: Cytokine arrays reveal “Black Ops” tactics of tumor-induced immunosuppression

Time : 11:15-11:35

Speaker
Biography:

Ruo-Pan Huang is a founder and CEO of RayBiotech, Inc and adjunct Associate Professor of Emory University. As a pioneer in the development of protein array technology, he and his team have developed many innovative protein array technologies and products which now are widely used worldwide by many investigators. He has published about 100 scientifi c research papers. He also serves on the editorial board of several journals such as Cancer Genomics and Proteomics, journal of analytical oncology and open journal of proteomics and on several other committees, including an NIH study section and Chinese National Natural Science Fund. His research has been funded by NIH, ACS, Emory University and others. During his tenure, he has received several awards, including the American Cancer Society Young Investigator Award.

Abstract:

The immune system continuously scans for foreign substances on pathogens and aberrant cells and targets them for elimination. To persist and grow, tumors must evade or sabotage this constant immunosurveillance. The mechanisms of innate and adaptive immune response and of tumor-induced immunosuppression involve complex networks of many different cell types that are regulated and coordinated by numerous cytokines and other related secreted proteins. Much of our current understanding of these complex interactions have come through the dissection of cell–cell communication networks in the tumor microenvironment using multiplexed protein detection, such as cytokine antibody arrays, which can detect expression of dozens or hundreds of proteins in a single experiment. This presentation will give examples of the investigative power of cytokine antibody arrays to help identify key factors in complex biological mechanisms in conjunction with more classical methods of cellular and molecular biology. Additionally, a model of tumor-induced immunosuppression, suggested by the collective results of such experiments, will be presented along with the implications of this model for future investigations of cancer immunology.

Speaker
Biography:

Anwen S Williams is a Pharmacist, a member of the Royal Pharmaceutical Society and a senior member of the academic staff in the School of Medicine at Cardiff University. She is a biomedical research expert who is passionate about defining the biological changes that occur in the musculoskeletal system during the transition from health to disease. Her work has been supported by Arthritis Research UK, the Wellcome Trust, the British Heart Foundation, the Medical Research Charity and Joint action. Her sustained output of high quality research papers provide evidence of her scientific expertise that is aligned with (i) the development and characterization of models which recapitulate cellular, molecular and architectural features of inflammatory joint disease, (ii) the identification and examination of cellular and molecular mechanisms that orchestrate cell trafficking, inflammation-induced tissue injury and reparative responses and (iii) the evaluation of novel agents for treating arthritis.

Abstract:

The influence of complement-mediated innate immune responses on cartilage and bone homeostasis in the ageing joint has not been studied. Inappropriate complement-mediated cell damage is prevented by membrane regulators such as CD59. Synovial tissue expression of CD59 is altered during inflammatory arthritis; elevated CD59 levels may be necessary to protect joint tissues. Roles of CD59 in maintaining tissue equilibrium and structural architecture within the synovial joint have not been described previously. Since CD59a is the primary regulator of membrane attack complex assembly in mice; we used CD59a-gene-deleted mice (CD59a-/-) as tools to unravel the function of CD59a in modulating inflammatory arthritis, bone re-modelling and age-related joint degeneration. Inflammatory and degenerative changes are classified using histopathology whilst three dimensional radiological image analysis provided objective markers of bone changes at the tibiofemoral joint.

Biography:

Distinguished Professor Ru-Band Lu graduated from National Defense Medical center Taipei, Taiwan, in 1972. He became a professor of Psychiatry at National Defense Medical Center in 1989. 1992 to 1993, he was a visiting scientist in Human Genetics at Yale University, New Haven, CT; he studied genetics, psycho-neuroimmune pharmacology. 2003 to 2009, he was the director of the Institute of Behavioral Medicine, National Cheng Kung University, Tainan, Taiwan. In this decade, he works in the developmental navel treatment model. He has published more than two hundred research articles in the recent fifteen years

Abstract:

Over activation of inflammatory cytokine and dysfunction of neurotrophic system have been associated with the progression of heroin dependence. Both memantine and dextromethorphan (DM) belong to non-competitive NMDA receptor antagonist, but low dose memantine/DM might possess anti-inflammatory and neurotrophic effects that are mechanistically remote from an NMDA receptor. A randomized, double-blind, placebo-controlled 12-week study was conducted. Heroin dependence patients undergoing regular methadone maintenance therapy were randomly assigned to a group: Memantine (5 mg/day), DM (60~120 mg/day) or Placebo. Inflammatory markers and neurotrophic factors including plasma TNF-, CRP, IL-6, IL-8, TGF-β1, and BDNF levels were examined during weeks 0, 1, 4, 8, and 12. After treatment, significantly inhibition of tolerance to methadone was found in both in patients received memantine/DM compared to the placebo group; decreased methadone required dose was found in patients received memantine compared to the placebo group. In addition, significantly reduced plasma tumor necrosis factor-α (TNF-α) was found in both in patients received memantine/DM compared to the placebo group while increased TGF-β1was found only in the memantine group. Significantly increased BDNF level was only detected in patients received DM compared to the placebo group. We suggest that low-dose memantine/DM might be a feasible adjuvant therapy for attenuating inflammation, providing neuroprotection, and inhibiting methadone tolerance in heroin dependent.

Elena Gavrilova

OOO NPF Materia Medica Holding, Russia

Title: Application of drugs based on release-active antibodies as immunotherapy agents

Time : 12:15-12:35

Speaker
Biography:

Elena S Gavrilova is working under her PhD at Institute of pharmacology of Tomsk scientific center of Russian Academy of Medial Science. She is a research associate and a leader of immunoassay group in Research & Analytical department of OOO "NPF "MATERIA MEDICA HOLDING", Moscow. Elena Gavrilova underwent a study course in immunoassay techniques at AB Biotechnology (Edinburgh, UK). She has published 10 papers in reputed journals (including two articles in English).

Abstract:

High efficacy of antibodies (Abs) preparation has made Abs-based drugs widely represented among marketed medicinal products. However, despite their popularity, the use of Abs-based agents is challenged due to limitations in oral availability and problems with stability and toxicity. Phenomenon of release activity (RA) was launched by Oleg Epstein (Epstein, 2013). He was the first who combined the approach of multiple circles of consecutive decrease in the substance’s initial concentration and physical treatment up to the desired dilution with the use of such biotechnological product as Abs. The technologically treated Abs were shown not to neutralize the targets, but to modify the interaction between the target and the respective endogenous molecule-regulator instead. As the activity of these modified Abs is different from that of the original Abs, they are called release-active Abs. Efficacy of release-active Abs-based drugs was shown in plenty of preclinical studies and in multicenter randomized double-blind parallel-group placebo-controlled or open label comparative randomized clinical trials. The drug’s high safety and lack of toxicity have been confirmed clinically and by extensive cellular and animals studies. Thus, drugs based on release-active Abs became the unique medicines which combine the high efficacy and safety and several of them are already presented on the market. These drugs showed great potential in treating the diseases eliciting an immune response (i.e. involving the process of inflammation, infection, etc) such as rheumatoid arthritis (Artrofon), viral infections (Anaferon for children, Anaferon and Ergoferon) as well as such diseases as diabetes mellitus (Subetta) and obesity (Dietressa).

Sylvie Bertholet

Novartis Vaccines and Diagnostics, Italy

Title: Reinventing the gene vaccine: Non-viral delivery of mRNA

Time : 12:35-12:55

Biography:

SBertholet is currently head of In Vivo Immunology at Novartis Vaccines & Diagnostics (NVD) Italy, responsible for the immunological characterization of next generation Staphylococcus aureus and influenza vaccines.She has over 20 years of experience in infectious diseases and vaccine development. She received her PhD in Immunology from the University of Lausanne, Switzerland,and completed her postdoctoral training at the University of Lausanne and at the National Institutes of Health in Bethesda, studying host-pathogen interactions. Prior to joining NVD, she held position at the Infectious Disease Research Institute in Seattle leading Tuberculosis, Pneumococcus and Leishmania vaccine development projects. She has authored more than 40 publications on infectious disease and vaccine-related topics.

Abstract:

Novartis has developed the SAM®vaccine platform.This platform, now in pre-clinical development, is based on a synthetic, self-amplifying mRNA, delivered by a synthetic lipid nanoparticle (LNP). The broad utility of this novel vaccine technology has been demonstrated with genes encoding vaccine candidate antigens from several pathogens and was found to elicit broad and potent protective immune responses in multiple animal models. Immune responses are comparable to a viral technology, but without the inherent limitations of viral vectors. Furthermore, the recent combination of rapid and accurate cell-free gene synthesis and SAM vaccine technology allowed the generation of a pandemic H7N9 vaccine candidate in one week from posting of the gene sequence on the CDC website. If the SAM vaccine platform proves safe and effective in humans, fully synthetic vaccine technologies could provide unparalleled speed of response to stem the initial wave of outbreaks, with a vaccine candidate ready days after the discovery of a new virus.

Baochi Liu

Shanghai Public Health Clinical Center Affiliated to Fudan University, China

Title: Treating AIDS patients with decompensated liver cirrhosis by autologous bone marrow transfusion

Time : 12:55-13:15

Speaker
Biography:

Baochi Liu received his Ph.D. from Zhengzhou University in 2007. He received his B.S.in 1983. He has many Peer-reviewed Publications in reputed journals. His research interest includes general surgery, surgery infection and trauma. He is currently working as a Director and Professor in Department of Surgery, Shanghai Publical Health Clinical Center Affiliated to Fudan University, Shanghai, China.

Abstract:

Background:
Decompensated liver cirrhosis is difficult to treat, liver cirrhosis with AIDS is more difficult to give effective treatment.Stem cell treatment bring the hope for the patients of AIDS with decompensated liver cirrhosis.
Methods:
splenectomy were performed in 8 AIDS patients with liver cirrhosis to alleviate portal ven hypertention and avoid internal blooding. During the surgical procedure, a catheter was placed in the superior mesenteric vein in preparation for bone marrow transfusion (BMT). 20mL bone marrow was aspirated by puncture of the iliac crest (spina iliaca posterior superior) one week after surgery and transfused through the attached catheter into the portal vein. One or two doses of BMT were performed on each patient at a one month interval.
Result:
Except diminishment of ascites and recovery of serum albumin levels, total white blood cells and platelet count was also significantly improved. Unexpectedly, one month after BMT, CD4+ T cell count in peripheral blood of all 8 patients began to increase significantly. Conclusion: BMT for the AIDS patient with liver cirrhosis can promote liver function and immune reconstrauction.

Break: Lunch Break 13:15-14:00 @ Eden’s Landing Restaurent
Biography:

Elena Fridman obtained her M.D. from Technion –the Israel Institute of Technology in 2006, and received her M.Sc. in Genetics from the Tel Aviv University, Israel,studying the Pemphigus Vulgaris associated HLA genes in Jewish patients. She completed her pediatric residency at the Schneider Children's Hospital, Israel, and joined the Neonatal department at the Rabin Medical Center, affiliated to Tel Aviv University, in November 2012. Her research has been published in peer reviewed scientific journals and presented in national/international scientific meetings.

Abstract:

Extensive research in a relatively young scientific discipline called photoimmunology is constantly revealing new insights into the immunomodulatory effects of ultraviolet radiation (UVR) from sunlight and of vitamin D. Evidence from up to date studies suggests that exposure to UVR and vitamin D deficiency are associated with immunosuppression and an increased susceptibility to infection, along with a diminished reaction to some types of vaccinations. Ultraviolet radiation is known to adversely affect the immune system, hence its use in the context of an overactive immune system (e.g. autoimmune disease) via immunosuppression. Along with its harmful side effects, UVR is likely to lead to an increased vitamin D status. Vitamin D is fundamental for a positive immunomodulatory function that, probably, outweighs the negative effect of UVR, which is limited mainly to the approximately 48 hours post exposure and can be controlled with proper precautions. Recent studies have demonstrated that vitamin D deficiency is related to infection severity, including increased length of hospitalization stay and increased mortality in those admitted to intensive care units. Conversely, no consistent protective properties of vitamin D supplementation were evident in prospective clinical trials, except for vitamin D deficient individuals. Thus far, dietary vitamin D supplements have not been found to enhance the immune response to vaccines, and the inoculation rate is not determined by vitamin D status. The myriad of mechanisms that mediate UVR induced immune-modulation is complex and controversial. The suppressive and the stimulatory influences of UV radiation and vitamin D on the immune system, conjoint or independent, are key factors in achieving optimal immunogenicity. This issue is of special concern given the constantly increasing amount of radiation in our atmosphere. Prospective public health implications regarding routine vaccination scheduling and policies; as well as sunscreen modalities for preventing UVR-induced damage are further discussed.

Biography:

Vineeta V. Deshmukh is Deputy Director of Integrated Cancer Treatment and Research Centre of Ayurved Hospital and Research Centre, Wagholi, Pune, India, which is recognizedas “Centre of Excellence” by Department of AYUSH, Government of India. She is a Professor of Department of Basic Principles inAyurved College, Wagholi. She is a guide for M.D. and Ph.D. (Ayurved). She has completed her M.D. from Mumbai University and Ph.D. from Pune University. She has participated many National and International conferences and presented research work on Cancer and AIDS. She has published 3 research papers in peer review International journals on efficacy of Ayurvedic treatment in cancer and HIV – AIDS.

Abstract:

Ayurveda, an ancient Indian system of medicine is practised even today for various illnesses especially those which are caused by reduced immune responses. Recently combinations of Ayurvedic drugs are recommended for cancer as an adjunct therapy. In the first part of this study we have clinically assessed the efficacy of Ayurvedic drugs in alleviating side effects of radiotherapy. In the second part, we have undertaken additional studies to assess the improvement in immune status of these patients. In both studies the assessment was done before, after completion of radiotherapy and one month thereafter. 70 Patients of oropharyngeal cancers with all stages and grades of the disease, who opted for radiotherapy, were enrolled for the first part of the study. Group 1 consisted of 35 patients who were treated with radiotherapy alone while Group 2 consisted of 35 patients who received combinations of Ayurvedic drugs. Ayurvedic treatment consisting of following 4 preparations was given daily for Group 2 patients during 5 weeks of radiotherapy and 4 weeks thereafter. 1) Mauktikyukta Kamadudha 2) Mauktikyukta Praval Panchamrut (Herbo-mineral mixtures) and 3) Ananta Vati (Tablet of Hemidesmus indicus) were given orally twice a day, while 4) Yashtimadhu Ghruta (Ghee medicated with liquorice) was given as local application twice daily. To assess the clinical efficacy of Ayurvedic drugs, we have used following criteria. A) Common toxicity criteria of radiotherapy - Stomatitis, Trismus, Dysphagia, Xerostomia, Nausea, Excessive salivation and Weight loss B) Karnofsky score- general well-being and activities of daily life C) ECOG numerical score (Eastern Cooperation Oncology Group) – general well-being and assessment of symptoms D) QLQ Scales (QLQ C 30) as per assessment criteria by EORTC (Symptom, Global and Functional scores) Results of this study show significant clinical improvement in stomatitis, trismus, dysphagia, xerostomia & nausea with p values varying between 0.004<0.0001. Also, Karnofsky and ECOG scores show significant improvement with p=0.003 & 0.002 respectively. Quality of Life (QLQ) data shows significant difference between the 2 groups with p<0.0001 in Functional, Symptom and Global scores. Therefore it was necessary to study whether the drugs are exerting immunomodulatory effect on the host which could be one of the reasons for the clinical improvements observed. To address this question, we have undertaken a pilot study on 15 patients with oropharyngeal cancers to assess the immune status of patients undergoing similar treatment. Samples of peripheral blood and saliva (for assessment of local immune response) are being collected at the time points mentioned above. Following immunological criteria are being assessed – A) Tumour markers in PB and saliva– Ki67, CD105 by Elisa B) Immunophenotyping - Total T&B cells and T cells subsets in PB by FCM C) Functional assays for T and B cells– Proliferation using mitogens PHA/PWM assessed by 3H Thymidine incorporation D) Assessment of proinflammatory and antiinflammatory cytokines (IL-1, IL-6, IL-8, TNF-α, IL-10, IFN-γ) by FCM E) Circulating immune complexes in saliva and PB by PEG precipitation F) Levels of IgA in saliva and PB by Elisa Results of studies on the immune parameters are expected to through some light on improvement in immune response in patients treated with Ayurvedic drugs, which will have implications in many other diseases as well.

Speaker
Biography:

Eman Hussien Abdel-Rahman is currently working as Professor in National Research Center, Dokki, Cairo, Egypt since 2005. In 1990, she was appointed as Assistant Researcher at the National Research Center, Dokki, Cairo, Egypt. In 1995, she was appointed as Researcher at the National Research Center, Dokki, Cairo, Egypt. In 2000, she was appointed as Associate Professor at the National Research Center, Dokki, Cairo, Egypt. In 2005, she was appointed as Professor at the National Research Center, Dokki, Cairo, Egypt. Eman Hussien Abdel-Rahman received her B.Sc. in Zoology in 1981 at Cairo University, Egypt. She got M.Sc. in Immunoparasitology in 1990 from Cairo University, Egypt. Dr. Eman Hussien Abdel-Rahman obtained Ph.D. from Cairo University, Egypt in 1995 in Immunoparasitology. Eman Hussien Abdel-Rahman’s current research interests are Immunoparasitology, Biological Control, DNA Technology, Glycoprotein Antigens, Parasitology.

Abstract:

Fasciolosis due to Fasciola gigantica or F.hepatica causes significant production losses in animals, as well as being a zoonotic disease of global importance. In an attempt to develop vaccine against fasciolosis in rabbits, an immunoaffinity fraction of F.gigantica excretory secretory products was isolated. The fraction possesses 87.67% of the initial antigenic activities in ES products with 2051.5 fold increase in specific activity compared to crude extract. It consists of two bands of molecular weight 27KDa and 23.5KDa as revealed by SDS-PAGE. Vaccination of rabbits twice with the fraction resulted in 85.7% reduction in worm burden. It is also resulted in high antibody IgG levels as proved by ELISA.Where the highest IgG response was observed at two weeks post first immunization compared to non-vaccinated infected control rabbits. The level of IgG increased at four weeks post infection and remained stable to the end of the experiment. A significant expression of IL-4 and INF-gamma was observed in vaccinated rabbits starting one week until thirteen weeks post infection. The level of IL-4 was significantly higher than the level of INF-gamma throughout the experiment. Collectively, the current results suggest promising immunoprophylactic potentials of the immunoaffinity fraction of ES products of F.gigantica against fasciolosis in rabbits through induction of both cellular and humoral responses.

Biography:

Lucia Gemma Delogu now is assistant professor and head of the laboratory of Bionanotechnology and Biochemistry at the University of Sassari, Italy. She got her BSc focusing on genetics and the Ph.D. on Biochemistry and molecular biology. She was post doctoral fellow at the University of Southern California, USA (2007-2009). She was visiting researcher at the National Institute of Health of Bethesda (USA) in 2013. Dr. Delogu got the title as “Best 200 Italian Talents” from the Italian Ministry of Youth in 2011, she got the “Del Prete: medicine, biology and nanotechnology Award in 2012” and “the Bedside to bench & Back Lecture Series Achievement Award” in 2013 at the NIH Bethesda, USA. She is part of the editorial board of Journal of Translational Medicine. Dr. Delogu’s laboratory focus on functionalized carbon nanotubes, graphene, superparamagnetic irone oxide nanoparticles and nanocapsules and their interaction with the immune system at the gene and protein level. Dr. Delogu also studies the different nanomaterials as potential ultrasound contrast agents.

Abstract:

Carbon nanotubes have been studied for a wide variety of applications included in medicine as drug delivery systems, targetable materials and diagnostic tools. Carbon nanotubes, toxic in their pristine forms, have been functionalized with many different techniques to make them biocompatible. We showed the potential use of well functionalized carbon nanotubes (f-CNTs) as ultrasound contrast agents (Delogu LG et al. PNAS 2012). We studied the interaction of f-CNTs and primary immune cells (Delogu LG et al Nanomedicine lond 2012) and, we proposed f-CNTs as immunomodulators showing their potential as activators of the immune systems (Pescatori M et al. Biomaterials 2013). Moreover, we recently evaluated the possibility of taking advantage of immunostimolatory properties of f-CNTs against microgravity immune function dysregulation (Crescio et al. Nanoscale 2014). Our results proved that the capacity of f-CNTs to stimulate immune cells have very interesting broad future applications not only in immunotherapy or as vaccine adjuvants, as we recently suggested, but also to contrast spaceflight immune cells functionality suppression. Results from different investigations, functionality assays and their potential as theranostic materials will be presented and discussed.

Speaker
Biography:

Ivan Mfouo-Tynga (Bachelor of Sciences in Human Physiology and Biochemistry, Bachelor of Technology in Biotechnology, Master of Technology in Biomedical Sciences, University of Johannesburg, South Africa) is a present Doctorate candidate at the Laser Research Center, Faculty of Health Sciences, University of Johannesburg. His current work focuses on the development of a photochemical and anti-cancer compound, the mechanisms that accompanied cell damage and understanding of diverse mode of cell death. He has previously published his works in accredited journals, presented at several international conferences and he is the laureate of two merit awards.

Abstract:

Organ systems need to be properly regulated and protected from detrimental invasion. Many mechanisms work together to maintain the mammalian integrity however some entities can bypass these mechanisms leading to damage and sometimes death. Cancer is an unregulated cell growth condition that can spread and invade surrounding normal cells and tissues. Cancer escapes defense and control mechanisms, causes cellular damage and loss of cellular activity. More than 90% of cancer-related deaths occur by spreading malignant cells to vital organs, a process called metastasis. Photodynamic cancer therapy (PDT) uses non-toxic photochemotherapeutic agents, Photosensitizer (PS), to initiate a light dependent reactive oxygen species (ROS) related to cell damage. ROS are associated with oxidative stress and consequent cytodamage induced by oxidizing and degrading cell components. ROS are also involved in immune responses where they stabilize and activate Hypoxia inducible and phagocytic factors.Phthalocyanines (Pc) are stable PSs with improved photochemical abilities and a sulfonated Zinc Pc(ZnPcSmix) was used to investigate photodynamic effects in a breast cancer cell linein vitro using a 680 nm diode laser at a fluence of 10 J/cm2.Flow cytometry using Annexin V- fluorescein isothiocyanate (FITC), a cell death immunosorbent assay (ELISA) and gene expression analysis following ZnPcSmix mediated PDT were performed to determine the induced cell death pathways. ZnPcSmixlocalizedin critical cellular organelles and apoptotic cells abounded after the treatment. Nuclear fragmentation was seen as oligonucleosomal degradation and increased expression of the Bcl-2, DFFA1 and CASP-2 genes, indicated that apoptosis is the main induced mode of cell death.

Biography:

Mirette Hanna is about to accomplish her PhD studies in Experimental Medicine at Laval University. She is a Physician (medical degree obtained from Alexandria University) specialized in clinical pathology and blood banking. She has a Master degree in Clinical and Chemical Pathology from Ain Shams University. She has many papers and communications (around 10) in reputed journals and conferences.

Abstract:

Chronic inflammation plays a role in breast carcinogenesis. Local inflammation would be manifested by increased expression of pro-inflammatory markers [interleukin-6 (IL-6) or tumor necrosis factor-α (TNF-α)] to anti-inflammatory marker [transforming growth factor-β (TGF-β)] in breast tissue. It was assessed if local inflammatory state in breast tissue would affect the mammographic density, a breast cancer risk factor, among 82 premenopausal and 82 postmenopausal breast cancer patients. For each patient, six cores of normal breast tissue, located at >1.0 cm from the tumor, were extracted from mastectomy blocks and used to build up tissue microarray (TMA) blocks. TMA cut sections were stained by immunohistochemistry and digitized. The protein expression levels of inflammatory markers were visually estimated (intensity and proportion of positive cells) in normal epithelium present on digitized stained TMA sections. Quick score was obtained by multiplying the intensity by the proportion of positive cells. The pro- to anti-inflammatory marker expression ratios (IL-6/TGF-β and TNF-α/TGF-β) were calculated in three categories based on the quick score; anti-inflammatory (pro-inflammatory markeranti-inflammatory marker). Mammographic density was evaluated by a computer-assisted method. Associations were assessed by multivariate generalized linear models. Pro-inflammatory state of TNF-α/TGF-β among premenopausal women and IL-6/TGF-β among postmenopausal women were associated with higher percent mammographic density compared to the anti-inflammatory or the neutral state (p=0.014 and p=0.005, respectively). Affecting the expression of inflammatory markers in breast tissue may provide attractive targets for future breast cancer preventive strategies

Break: Coffee Break 16:00-16:15 @ Foyer
Biography:

Kathleen Hefferon received her PhD from the Department of Medical Biophysics, University of Toronto and continued her post-doctoral studies at Cornell University. Dr. Hefferon has worked on faculty at the Division of Nutritional Sciences at Cornell and has written two books on biopharmaceuticals in plants. She teaches and conducts research at both the University of Toronto and Cornell University. Kathleen has 4 patents, has edited 6 books, and has multiple research publications. Kathleen currently lives with her family near Ithaca NY.

Abstract:

Plant made biologics have elicited much attention over recent years for their potential in assisting those in developing countries who have poor access to modern medicine. Additional applications such as the stockpiling of vaccines against pandemic infectious diseases or potential biological warfare agents are also under investigation. Plant virus expression vectors represent a technology that enables high levels of pharmaceutical proteins to be produced in a very short period of time. Recent advances in research and development have brought about the generation of superior virus expression systems which can be readily delivered to the host plant in a manner that is both efficient and cost effective. The following presentation describes recent innovations in plant virus expression systems and their uses for producing biologics from plants.

Rahul Purwar

Indian Institute of Technology Bombay, India

Title: Engineered T cells: Next-generation cancer immunotherapy

Time : 16:35-16:55

Biography:

Rahul Purwar has completed his PhD from Hannover Medical School, Hannover, Germany and postdoctoral studies from Harvard Medical School, Boston, USA. He has worked for an Oncology company, ImmunoGen Inc. Waltham, USA before returning to India to join IIT-Bombay as an Assistant Professor. He has published several papers in reputed journals and has received many awards.

Abstract:

Cancer immunotherapy is an emerging and a transformative approach for the treatment of cancer patients. Although localized tumors especially breast cancer and skin cancer (melanoma) can be cured by surgical treatment, once cancer metastasizes, survival is limited. Immunotherapy is one of the best treatment options for patients with metastatic cancer, however benefits of available immunotherapy are limited because of following: 1) only a minor subgroup of patients show objective response to particular immunotherapy. 2) Current immunotherapy focuses on life-extension by only few months. Therefore, there is an urgent need of exploring novel strategies for the development of robust cancer therapy. Cancer of each patient is unique and personalized approach would be an ideal for successful cancer treatment: engineering immune-system that target antigen specific to each patient. Adoptive T cell therapy with engineered autologous T cells is unique and personalized for each patient and has potential for the eradication of cancer. Treatments with engineered CAR-T cells have generated some remarkable responses in patients with advanced cancer (acute lymphocytic leukemia patients and chronic lymphocytic leukemia (CLL) patients). Recently, we demonstrated that adoptive transfer of tumor-specific Th9 cells strongly inhibited melanoma tumor growth, and increased the duration of survival. Th9 cells inhibited melanoma growth in both normal and lymphopenic hosts, through both IL-9 dependent and independent pathways. More importantly, Th9 cells were superior in controlling tumor growth compared to other T cells. In conclusion, adoptive T cell therapy of cancer using engineered T cells comes of age and may provide effective cancer cure.

Biography:

Abstract:


Introduction:
Viral respiratory infections are the most common cause of an acute asthma exacerbation in both children and adults and represent a significant global health burden. They are found in approximately 80% of weezing episodes in school-aged children and ½ or ¾ of acute wheezing episodes in adults, 2010 Viral infections implicates in asthma development in many stages: 1. Resp. virus infections in infancy is a risk factor for, and may predispose to, the development of asthma later in life; 2. Resp. virus infection is associated with the acute exacerbation of bonchial asthma; 3. Glucocorticoids are not adequate for controlling asthma-related symptoms upon resp. virus infection.
Material and Methods:
Our study is a comparative clinical research, done in the University Clinical Center in Prishtina and in cooperation with specialized allergologic center Ylli in Prishtina. The including criteria was: 60 adult patients diagnosed with allergic asthma (Intermitent mild, Mild persistent, Moderate persistent Asthma (according to GINA) aged between 15 and 30 years, both sexes. 30 patients are treated with specific Immunotherapy (SCIT) and 30 of them with another anti-asthmatic drugs.
Results:
The number of patients who visited the physician for bronchial hyperactivity (BH) depends on whether they were on immunotherapy or not p=0.0001. In the first quarter, both groups are identified to have an equal number of coldness conditions. In the second quarter, a decreased frequency of coldness conditions is registered, in the group with immunotherapy 3/30 (10%), whereas in the group without immunotherapy that number was greater 11/30 (36%). In the third and fourth quarter the percentage of coldness condition of 3% has retained in the immunotherapy group, whilst in the group without immunotherapy there was an increase from 20/30 (66%) to 27/30 (90%).

Speaker
Biography:

I was graduated very good with honor November 1997 from faculty of medicine Tanta University, Egypt then Msc in clinical oncology, Tanta University, Egypt 2004 after that MD in clinical oncology, Tanta University, Egypt 2010 I worked firstly as Resident in clinical oncology Department, Tanta university hospital, Egypt from July 1999 to July 2002. Then as demonstrator in clinical oncology department- faculty of medicine- Tanta University till July 2004. After that I worked as assistant lecturer of clinical oncology, University, Egypt 2004 till 2010. Now I am working as Lecturer of clinical oncology, Tanta University, Egypt from 2010 till present.

Abstract:


Back ground and aim:
Prognosis of hepatocellular carcinoma (HCC) is very poor and determining the prognosis rely many factors and we aim at defining the prognostic factor of macrophage migration inhibitory factor (MIF) , P53 and its correlation with other prognostic factors in HCC. Patients: Serum macrophage migration inhibitory factor and anti-p53 antibodies were measured in 139 patients diagnosed with HCC using a specific enzyme-linked immunosorbent assay (ELISA) kit. The clinicopathological characteristics of the patients were compared with respect to the presence of serum anti-p53 antibodies.
Results
In univariate analysis, the prognostic factors with statistical significance were portal vein thrombosis, total serum bilirubin, serum albumin, serum AST, serum ALT, Prothrombin time , viral marker and anti p53 antibody and on multivariate analysis the prognostic factors were anti p53 antibody. Conclusion: Anti p53 antibody are associated with poor prognosis in HCC and it increased the prognostic potential of alpha fetoprotein. So p53can be used as target on HCC.

Speaker
Biography:

Abstract:

Rotavirus infection is the most common cause of acute diarrheal diseases among infants and young children worldwide. This work investigated whether cyclosporin A (CsA) combined with gentacimin inhibits human Wa rotavirus replication in HT-29 cells and in neonate BALB/c mice model. CsA combined with Gentacimin after Wa rotavirus infection significantly suppressed virus replication/infection, which is evidenced by reduced rotavirus antigen, decreased expression of rotavirus RNA, protein and infectious viruses in intracellular and extracellular. The inhibition of Wa rotavirus replication/infection by CsA combined with gentacimin can restore the expression of IFN-β in HT-29 cells. And CsA combined with gentacimin treatment of Wa rotavirus-infected HT-29 cells upregulated the expression of IFN regulatory factor-5, 7 and β-transducin repeat containing protein and inhibited the expression of suppressor of cytokine signaling-1, protein inhibitor of activated signal transducers and activators of transcription-1 and y, the primary negative regulators of IFN signaling pathway. CsA combined with gentamicin treatment of Wa rotavirus-infected-neonate mice shortened the recovered time against Wa rotavirus infection and speeded up the elimination of rotavirus antigen. These findings indicate that further evaluation and characterization of the CsA combined with gentacimin on Wa rotavirus-infected diarrhea are warranted.

Break: Panel Discussion 17:55-18:15

18:30-19:30 Cocktails sponsored by Journal of Clinical & Cellular Immunology