Browsing by Subject "immune system"
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Item Activation of Dendritic Cell Function by Soypeptide Lunasin as a Novel Vaccine Adjuvant(Office of the Vice Chancellor for Research, 2015-04-17) Simmons, Sharena J.; Tung, Chun-Yu; Chang, Hua-ChenThe innate immune system is the first line of defense against intruding pathogens. Dendritic cells (DCs) act as messengers between the adaptive and innate immune system, which process and present antigens to mature T helper cells (CD4+T), and Cytotoxic T cells (CD8+T). The addition of an appropriate adjuvant that activates the innate immunity is essential to subsequent development of the adaptive immunity specific to the vaccine antigens. Thus, any innovation capable of improving the immune responses may lead to a more efficacious vaccine. We recently identified a novel immune modulator using a naturally occurring seed peptide called lunasin. Lunasin was originally isolated from soybeans, and it is a small peptide containing 43 amino acids. Our studies had revealed stimulatory effects of lunasin on innate immune cells by regulating expression of a number of genes that are important for immune responses. The objective was to define the effectiveness of lunasin as an adjuvant that enhances immune responses. Immunization of mice with ovalbumin (OVA) and lunasin inhibited the growth of OVA-expressing A20 B-lymphomas, which was correlated with OVA-specific CD8+ T cells. Increased levels of anti-OVA IgG were also observed in mice immunized with OVA and lunasin. These results suggest that lunasin may function as a vaccine adjuvant by promoting DC maturation, which in turn enhances the development of protective immune responses to the vaccine antigens.Item ENHANCING THE TUMOR FIGHTING CAPACITY OF NK CELLS THROUGH THE USE OF SOYPEPTIDE(Office of the Vice Chancellor for Research, 2012-04-13) Lewis, David; Chang, Hua-Chen; Han, Ling; Voiles, Larry; Henriquez, Sarah M.P.Natural killer or (NK) cells are important components of the innate immune system, which play a major role in the rejection of tumors, and virally in-fected cells. By producing pro-inflammatory cytokines such as IFN-gamma, NK cells are able to exert immunoregulatory functions that influence the adaptive immunity of other immune cells. Due to its critical role in tumor inhibition, researchers, utilizing various cytokines, including IL-12 and IL-2, have fervently pursued the manipulation of NK activity. NK cells respond to cytokines in a dose-dependent manner; however, the toxicity of certain cy-tokines (like IL-2) in high doses prohibits their widespread clinical use. Therefore, efforts to activate NK cells without requiring high doses of cyto-kines is warranted. We recently exploited a soy derived dietary peptide called lunasin to improve the immune functions. The hypothesis was that the lunasin peptide has stimulatory effects on immune cells. To test this hy-pothesis, human peripheral blood mononuclear cells (PBMCs) of healthy do-nors were stimulated with and without lunasin in combination with cytokines IL-12 or IL-2. Our results showed that the lunasin peptide exerts a robust synergistic effect when combined with the selected cytokines. This effect ap-pears to regulate the expression of a number of genes that are important for NK activity. Our findings support the potential clinical use of lunasin in com-bination with cytokine to enhance the tumor fighting capacity of NK cells.Item Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility(Nature Publishing Group, 2015-04-23) Yin, Xianyong; Low, Hui Qi; Wang, Ling; Li, Yonghong; Ellinghaus, Eva; Han, Jiali; Estivill, Xavier; Sun, Liangdan; Zuo, Xianbo; Shen, Changbing; Zhu, Caihong; Zhang, Anping; Sanchez, Fabio; Padyukov, Leonid; Catanese, Joseph J.; Krueger, Gerald G.; Duffin, Kristina Callis; Mucha, Sören; Weichenthal, Michael; Weidinger, Stephan; Lieb, Wolfgang; Foo, Jia Nee; Li, Yi; Sim, Karseng; Liany, Herty; Irwan, Ishak; Teo, Yikying; Theng, Colin T. S.; Gupta, Rashmi; Bowcock, Anne; De Jager, Philip L.; Qureshi, Abrar A.; de Bakker, Paul I. W.; Seielstad, Mark; Liao, Wilson; Ståhle, Mona; Franke, Andre; Zhang, Xuejun; Liu, Jianjun; Department of Dermatology, IU School of MedicinePsoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations.Item Modulating NK-mediated Immunity by Lunakine(Office of the Vice Chancellor for Research, 2014-04-11) Chang, Hua-Chen; Tung, Chun-Yu; Lewis, David; Han, Ling; Srinivasan, Mythily; Robertson, Michael J.; Yeh, Wu-KuangDespite the plethora of immune modulating agents available in cancer treatment, their effectiveness relies on a functional immune system. However, the adverse side effects by chemotherapy impede the therapeutic benefits from immunotherapy. It remains a major challenge to prevent relapse for cancer patients who have already undergone rigorous chemotherapy. Lunasin, a 43-amino acid peptide, was originally isolated from soybeans. Our team has recently discovered a novel function of lunasin as an immune modulating agent that exerts robust synergistic effects imposed by several therapeutic cytokines. Such synergism strongly augments IFNγ and granzyme B expression by Natural Killer (NK) cells, which is associated with increased tumoricidal activity. The combination regimen with lunasin and cytokine is capable of restoring NK activation from lymphoma patients with chemotherapy-induced immune dysfunction. Our results support the potential application of lunasin to improve the therapeutic effects of existing cytokine treatment that has been used to eliminate residual tumors cells from lymphoma patients after chemotherapy. We designate lunakine as new formulation by combing lunasin and selected cytokine (filed for US Patent Cooperation Treat). In working with Indiana University and Technology Corporation (IURTC), we have started a startup company, Immune Peptide Therapeutics (IPT), LLC. Our mission is to develop a more efficacious immunotherapy that prevents relapse and confers progression-free survival for cancer patients. With the support from FORCES, our team has successfully developed a second generation of lunasin called IPT.103 that deviates from its parental type. Activity of IPT.103 has been tested in vitro with EC50 of 0.78 μM as compared to 4.54 μM for lunasin, indicating an improved potency to induce IFNγ production by NK cells. The newly developed peptide IPT.103 is expected to strengthen the intellectual property (IP) position for commercialization. We are currently working on tumor models for preclinical assessment of IPT’s regimens in immunotherapy for lymphoma.Item Understanding the immune system and how it works(2003-09) National Institute of Allergy and Infectious Diseases (U.S.); National Cancer Institute (U.S.)Background information on the immune system and its relation to cancer. Includes an extensive glossary.