6^th International Conference and Expo on Immunology October 24-25, 2016 Chicago,IL, USA

Biography:

Yong Ying has completed her Medicine degree from Shanghai Second Medical University, Shanghai China and was a Physician. She has worked for Children’s Hospital of Los Angeles, University of Southern California, School of Medicine, Abbott Laboratories and currently employed by Genentech as a Senior Scientific Researcher since 9 years.

Abstract:

PK characterization is a key step in the drug development process. In preclinical studies approximately 40% of therapeutic monoclonal antibodies (mAbs) tested in cynomolgus monkeys has atypically fast clearance. There are currently efforts to understand and mitigate the lead selection process to improve translational success in the clinic. One approach has been to investigate how antibody variable fragment (Fv) charge impacts PK and bioavailability of therapeutic antibodies. An empirical model was used to test the role of antibody Fv charge on PK properties by systematic amino acid substitutions in the Fv region of two mAbs, rhuMAbX and rhuMAbY. We compared the PK results of the parental mAbs and Fv charge variants to test our prediction for non-specific clearance. Given the large number of samples and low volumes we selected the Gyros platform for PK assay development and sample analysis. PK assays were developed and qualified successfully for the two parental mAbs and their two variants in three preclinical species (Cynomolgus monkey, Rat and Mouse). We present our results as well as our strategy in utilizing micro-sampling and the Gyros technology as a cost and time effective approach to streamline and improve efficiency for screening and selection of therapeutic mAb lead candidates for clinical development.

Biography:

Jeong-Eun Huh working in the Research Center for Cellular Homeostasis in Ewha Womans University. A major in molecular and cellular bone biology, she has published 3 peer-reviewed paper. Her primary research interests are in the field of osteoimmunology, especially the mechanisms of osteoclastogenesis. She received a research fellowship grant from the National Research Foundation of Korea (NRF). Her long term goal is to target signaling pathways as a novel approach to therapy.

Abstract:

The mitochondrial sirtuin 3 (SIRT3) is involved in suppressing the onset of multiple pathologies, including cardiovascular disease, fatty liver, breast cancer and age-related disorders. However, its role in bone metabolism is not known. Here we show the involvement of SIRT3 in osteoclast differentiation. Receptor activator of nuclear factor-κB ligand (RANKL), an essential cytokine for osteoclastogenesis, induces the expression of both the transcription co-activator peroxisome proliferator-activated receptor-γ co-activator-1β (PGC1β) and the nuclear receptor estrogen receptor-related receptor α (ERRα), which coordinately up-regulated SIRT3 during osteoclast differentiation from bone marrow-derived monocytes/macrophages (BMMs). SIRT3-deficient mice exhibit decreased bone mass compared with wild-type mice due to increased numbers of osteoclasts. Consistently, Sirt3^-/- osteoclast precursor cells underwent increased osteoclastogenesis in response to RANKL, whereas SIRT3 overexpression in osteoclast precursor cells exhibited reduced the formation of osteoclasts. Strikingly, Sirt3^-/- osteoclast precursor cells reduced AMP-activated protein kinase (AMPK) phosphorylation through down-regulating the expression of AMPK that plays a key role in regulating cellular energy metabolism during RANKL-induced osteoclast differentiation. These data demonstrate that a mitochondrial SIRT3 is an intrinsic inhibitor for RANKL-mediated osteoclastogenesis.

Biography:

Hyung-Ran Kim has completed her PhD from Yonsei University and Postdoctoral studies from Ewha Womans University School of Medicine. She is a Research Professor of Department of Microbiology. She has studied regulatory T cells and their own activity for suppression of immune responses.

Abstract:

Reactive oxygen species (ROS) have been considered harmful to tissues and as mediators of inflammation at the injury sites for a long time. However, in recent, many findings about other functions of ROS and oxygen are reported. The effects of ROS such as suppression of autoimmune disease and allergen-induced inflammation have been studied. Moreover, regulatory T cell (Treg) effects to various diseases including autoimmune and inflammatory diseases depending on own activity. There are also many reports on the therapeutic effects of hyperbaric oxygen therapy (HBOT) in chronic inflammatory or autoimmune diseases. We hypothesized that HBOT may improve arthritis symptoms. DBA1/J mice were used for entire experiments. Arthritis was induced by bovine type II collagen. HBOT protocol is 100% O₂ and 3 atm for 90 min after 30 min of compression and then followed by 45 min of decompression daily. We detected paw thickness by macroscopic anatomy and histological score by hematoxylin & eosin staining. Type II collagen antibodies and rheumatoid factors in serum were detected by ELISA. Expressions of some molecules related with Treg and oxygen were detected by immunoblotting. HBOT relieved paw thickness and decreased collagen antibodies and rheumatoid factors in serum. HBOT also reduced inflammation of synovial tissue. HBOT decreased protein expression of p-STAT3 and HIF-1α and increased that of IDO and FoxP3 in paw tissues of murine arthritis model. These data indicate that HBOT attenuated arthritis in DBA1/J mice through activation of Treg and regulation of some molecules related oxygen.

Biography:

Abstract:

RBJ has been identified to be dysregulated in gastrointestinal cancer and promotes tumorigenesis and progression by mediating nuclear accumulation of active MEK1/2 and sustained activation of ERK1/2. Considering that nuclear accumulation and constitutive activation of MEK/ERK not only promotes tumor progression directly but also induces chronic inflammation, we wonder whether and how RBJ impairs host immune-surveillance via chronic inflammation and consequently supports tumor progression. Here, we report that higher expression of RBJ in human breast cancer tissue has been significantly correlated with poorer prognosis in breast cancer patients. The forced expression of RBJ promotes tumor growth and metastasis both in vitro and in vivo. In addition, more accumulation of immune suppressive cells but less anti-tumor immune cell sub-populations were found in spleen and tumor tissue derived from RBJ force-expressed tumor-bearing mice. Furthermore, forced RBJ expression significantly promotes tumor cell production of pro-inflammatory cytokine IL-6 by constitutive activating MEK/ERK signaling pathway. Accordingly, RBJ knockdown significantly decreases tumor growth and metastasis in vitro and in vivo with markedly reduced production of IL-6. Administration of anti-IL-6 neutralizing antibody could reduce MDSCs accumulation in tumor tissue in vivo. Therefore, our results demonstrate that RBJ-mediated nuclear constitutive activation of ERK1/2 leads to persistent production of IL-6 and increase of MDSCs recruitment, contributing to promotion of tumor growth and metastasis. These results suggest that RBJ contributes to tumor immune escape, maybe serving a potential target for design of antitumor drug.

Biography:

Abdulrahman Khazim Al-Asmari is known for his scientific contributions in the field of toxinology. At present he is undertaking research projects to study the natural toxins such as the venoms of scorpion and snakes and their different fractions for treating different diseases including cancer.  He is the author and coauthor of more than 50 publications which were published in reputed international and national journals. He is also the author of several books and book chapters published by International publishers of repute. He is a member of the Editorial Board of many journals of prestigious national and international scientific societies and committees.

Abstract:

Scorpion venoms efficiently block the neurotransmitter signaling pathway by prejudicing the ion channel operating mechanism in the body system. This massive effect of ion channel impairment by the venom is due to the presence of various macromolecules such as proteins and peptides in it. Beside its negative effect, venoms also possess some of the beneficial aspect for the human being. The venom has also been shown to exhibit anti-cancer properties in various cancer types. This unique property of the venom as anti-cancer agent is mainly due to its role in creating apoptosis and also inhibiting several signaling cascade mechanism which promotes cancer cell proliferation and growth. In this study we examine the effect of venom (obtained from our local serpentarium facility) on the phenotypic changes as well as change at the molecular levels in colorectal and breast cancer cell lines. A dramatic decrease in cell invasion was observed in both the cancer cell lines upon venom treatment. We observed 60-90% decrease in this parameter which is an important hallmark of cancer progression. Additionally, a decrease in IL-6 as well as in RhoC expression indicates anti-cancer properties of the venoms used in this study. Additionally, decrease in the phosphorylation of Erk^1/2 and STAT3 gives strong messages of its anti-cancer properties. In addition to this, decrease in the expression of pro-apoptotic proteins such as Bcl2 (Bcl-X_L) and BID and up-regulation of anti-apoptotic/tumor suppressor protein (p⁵³) by the colorectal and breast cancer cell lines when treated with venoms indicates its role as a pro-apoptotic agent. In addition to this, a vivid picture of DNA damage in comet assay was also observed in venom treated cell lines. Our study is in agreement with the previous work showing the anti-cancer property of scorpion venom. In conclusion, the scorpion venom obtained at our research center at Prince Sultan Military Medical City (PSMMC) possesses significant potential to act as an anti-cancer agent against colorectal and breast cancer cell lines.

Biography:

Fanny Chmilewsky has completed her PhD in 2013 from Aix-Marseille University and currently doing postdoctoral research from University of Illinois at Chicago College of Dentistry. She has exemplary training in pulpal biology with expertise in pulp regeneration and complement system research. She has published her research in very reputed journals such as Journal of Dental Research and American Journal of Pathology.

Abstract:

Given the importance of sensory innervation in tooth vitality, the identification of signals that control nerve regeneration and the cellular events they induce is essential to identify new therapeutic targets. The complement anaphylatoxin C5a, which is one of the very first components of innate immunity and inflammation is produced at the injured site of human carious teeth and plays an important role in dental-pulp regeneration via interaction with nearby dental pulp cells­. We extend these observations in dental nerve regeneration research with regard to local production of neurotrophins by pulp fibroblasts upon carious injury. Recently we demonstrated that caries-associated C5a receptors (C5aR) expression is followed by its activation by the C5a generated from the activation of complements molecules expressed by pulp fibroblasts. C5aR signaling results in brain-derived nerve growth factor (BDNF) secretion by pulp fibroblasts that induces prominent neurite outgrowth toward the site of carious injury. Previously another C5a receptor, C5L2, has been identified. Since no signaling pathway is induced following its interaction with C5a, it received very little attention. In this study, our results further demonstrate that newly generated C5aR in human pulp are co-localized with C5L2 both in vivo and in vitro shortly after carious injury. Furthermore, C5L2 siRNA-silencing significantly increased BDNF-secretion in LTA-stimulated pulp fibroblasts. Thus the C5aR and C5L2 studies in the regenerative process could provide innovative therapeutic strategy, i.e., the possibility to enhance and/or prolong the positive action of C5a in dental pulp regeneration by activating or blocking these active and inactive receptors.

Biography:

Bakaeva Zanda Valerievna has completed PhD and postdoctoral studies from Department of Human and Animal Physiology, Faculty of Biology, Lomonosov Moscow State University. She is the senior researcher of Laboratory of Neurobiology, Scientific Center of Children's Health of the Russian Federation Ministry of Health. She has published more than 25 papers in reputed journals. She is the docent at the Department of Physiology People’s Friendship University of Russia.

Abstract:

Cytokines plays an important role in the development and course of diseases of different systems, including the digestive system. Lymphocytes of regional lymph nodes are the main sources of cytokines which are involved in inflammation. We compared systemic and local cytokine profile of rats with acetate ulcer (AU). Blood was collected from the jugular vein of the rats on the day 4 and 7 after acetate-induced ulceration. Max. AU – after 3 days, 10 days formed scar.  ln. gastricus caudalis of rats were used as the source of T-lymphocytes. Cytokine’s levels were determined in the serum and in the supernatant of mitogen-activated mononuclear cells by flow cytometry. The max. concentration of IL-1α and MCP-1 in the serum of rats without ulcers (IR) was 61.9±15.1 pg/ml and 537.2±82.2 pg/ml resp. Other cytokines were <10 pg. The AU formation induced a significant increase of IL-1α and MCP-1 in the serum in 2.2 and 13.5 times. The level of the other cytokines did not change. The max. of IL-1α, MCP-1, IL-17α, IFNg, IL-4, TNFα in the supernatant of lymph node cells were equal to 273.0±24.6, 62.7±8.7, 2852.8±146.5, 1115.9±168.8, 598.9±33.8, 87.5±18.1 pg/m, resp. AU formation was accompanied by an acute shortage of all local cytokines. This continued on the day 7, expressly were low IL-1α and MCP-1, alone IL-17α reverted to normal. So, despite that the development and healing of AU were accompanied by high content in serum of basic proinflammatory cytokines, contrary local immunity is suffer from their deficiency. At help comes IL-17α.