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Interleukin-15

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https://www.readbyqxmd.com/read/29769573/discovery-of-a-novel-il-15-based-protein-with-improved-developability-and-efficacy-for-cancer-immunotherapy
#1
Qiyue Hu, Xin Ye, Xiangdong Qu, Dongbing Cui, Lei Zhang, Zhibin Xu, Hong Wan, Lianshan Zhang, Weikang Tao
Interleukin-15 (IL-15) can promote both innate and adaptive immune reactions by stimulating CD8+ /CD4+ T cells and natural killer cells (NK) while showing no effect in activating T-regulatory (Treg) cells or inducing activation-associated death among effector T cells and NK cells. Thus, IL-15 is considered as one of the most promising molecules for antitumor immune therapy. To improve the drug-like properties of natural IL-15, we create an IL-15-based molecule, named P22339, with the following characteristics: 1) building a complex of IL-15 and the Sushi domain of IL-15 receptor α chain to enhance the agonist activity of IL-15 via transpresentation; 2) through a rational structure-based design, creating a disulfide bond linking the IL-15/Sushi domain complex with an IgG1 Fc to augment its half-life...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29754714/membrane-potential-distinctly-modulates-mobility-and-signaling-of-il-2-and-15-receptors-in-t-cells
#2
Éva Nagy, Gábor Mocsár, Veronika Sebestyén, Julianna Volkó, Ferenc Papp, Katalin Tóth, Sándor Damjanovich, György Panyi, Thomas A Waldmann, Andrea Bodnár, György Vámosi
The high electric field across the plasma membrane might influence the conformation and behavior of transmembrane proteins that have uneven charge distributions in or near their transmembrane regions. Membrane depolarization of T cells occurs in the tumor microenvironment and in inflamed tissues because of K+ release from necrotic cells and hypoxia affecting the expression of K+ channels. However, little attention has been given to the effect of membrane potential (MP) changes on membrane receptor function...
May 10, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29737430/hil-15-gene-modified-human-natural-killer-cells-nkl-il15-exhibit-anti-human-leukemia-functions
#3
Wen Jiang, Cai Zhang, Zhigang Tian, Jian Zhang
PURPOSE: Natural killer (NK) cells can kill transformed cells and represent anti-tumor activities for improving the immunotherapy of cancer. In previous works, we established human interleukin-15 (hIL-15) gene-modified NKL cells (NKL-IL15) and demonstrated their efficiency against human hepatocarcinoma cells (HCCs) in vitro and in vivo. To further assess the applicability of NKL-IL15 cells in adoptive cellular immunotherapy for human leukemia, here we report their natural cytotoxicity against leukemia in vitro and in vivo...
May 8, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29700172/the-early-expansion-of-anergic-nkg2apos-cd56dim-cd16neg-natural-killer-cells-represents-a-therapeutic-target-in-haploidentical-haematopoietic-stem-cell-transplantation
#4
Alessandra Roberto, Clara Di Vito, Elisa Zaghi, Emilia Maria Cristina Mazza, Arianna Capucetti, Michela Calvi, Paolo Tentorio, Veronica Zanon, Barbara Sarina, Jacopo Mariotti, Stefania Bramanti, Elena Tenedini, Enrico Tagliafico, Silvio Bicciato, Armando Santoro, Mario Roederer, Emanuela Marcenaro, Luca Castagna, Enrico Lugli, Domenico Mavilio
Natural Killer cells are the first lymphocyte population to reconstitute early after non myelo-ablative and T cell-replete haploidentical hematopoietic stem cell transplantation with post-transplant infusion of cyclophosphamide. The present study characterizes the transient and predominant expansion starting from the 2nd week after haploidentical hematopoietic stem cell transplantation of a donor-derived unconventional subset of NKp46neg-low/CD56dim/CD16neg natural killer cells expressing remarkable high levels of CD94/NKG2A...
April 26, 2018: Haematologica
https://www.readbyqxmd.com/read/29699793/serum-interleukin-15-levels-in-patients-with-seropositive-myasthenia-gravis-do-not-correlate-with-disease-severity
#5
Ewa Sobieszczuk, Justyna Kubiszewska, Marta Lipowska, Piotr Szczudlik, Beata Szyluk, Małgorzata Dutkiewicz, Anna Kostera-Pruszczyk
AIM: To assess interleukin 15 (IL-15) serum levels in patients with seropositive myasthenia gravis (MG); searching for potential relationship between IL-15 levels and clinical features such as gender, age at onset, clinical presentation or treatment received. BACKGROUND: IL-15 plays pivotal role in T-cell dependent autoimmunity. Increased IL-15 serum levels have been reported in several autoimmune diseases including MG patients from Japan. PATIENTS AND METHODS: Sera of 42 seropositive MG patients (66...
January 6, 2018: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/29692776/interleukin-15-cultured-dendritic-cells-enhance-anti-tumor-gamma-delta-t-cell-functions-through-il-15-secretion
#6
Heleen H Van Acker, Sébastien Anguille, Hans De Reu, Zwi N Berneman, Evelien L Smits, Viggo F Van Tendeloo
Dendritic cell (DC) vaccination can be an effective post-remission therapy for acute myeloid leukemia (AML). Yet, current DC vaccines do not encompass the ideal stimulatory triggers for innate gamma delta (γδ) T cell anti-tumor activity. Promoting type 1 cytotoxic γδ T cells in patients with AML is, however, most interesting, considering these unconventional T cells are primed for rapid function and exert meaningful control over AML. In this work, we demonstrate that interleukin (IL)-15 DCs have the capacity to enhance the anti-tumoral functions of γδ T cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29685202/correlation-between-immunological-inflammatory-markers-and-endothelial-disfunction-in-the-early-stage-of-coronary-heart-disease
#7
Viktor Persic, Ana Lanca Bastiancic, Ivan Rosovic, Damir Raljevic, Dijana Travica Samsa, Luka Bastiancic, Rajko Miskulin, Marko Boban, Gordana Laskarin
Classical risk factors for endothelial dysfunction (ED), such as age, gender, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, and smoking history are utilised for the Framingham score and Systemic Coronary Risk Estimation (SCORE) for evaluation of the 10-year cardiovascular risk in routine practice. Nonetheless, pro-inflammatory mediators are deeply involved in the initiation and the progression of ED and coronary artery disease (CAD), and act additionally or independently of metabolic factors before clinical manifestations of the disease appear...
June 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29656472/in-vitro-and-in-vivo-characterization-of-an-interleukin-15-antagonist-peptide-by-metabolic-stability-99m-tc-labeling-and-biological-activity-assays
#8
Yunier Rodríguez-Álvarez, Ania Cabrales-Rico, Alejandro Perera-Pintado, Anais Prats-Capote, Hilda E Garay-Pérez, Osvaldo Reyes-Acosta, Erik Pérez-García, Araceli Chico-Capote, Alicia Santos-Savio
Interleukin (IL)-15 is an inflammatory cytokine that constitutes a validated therapeutic target in some immunopathologies, including rheumatoid arthritis (RA). Previously, we identified an IL-15 antagonist peptide named [K6T]P8, with potential therapeutic application in RA. In the current work, the metabolic stability of this peptide in synovial fluids from RA patients was studied. Moreover, [K6T]P8 peptide was labeled with 99m Tc to investigate its stability in human plasma and its biodistribution pattern in healthy rats...
April 15, 2018: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29625893/interleukin-15-complex-treatment-protects-mice-from-cerebral-malaria-by-inducing-interleukin-10-producing-natural-killer-cells
#9
Kristina S Burrack, Matthew A Huggins, Emily Taras, Philip Dougherty, Christine M Henzler, Rendong Yang, Sarah Alter, Emily K Jeng, Hing C Wong, Martin Felices, Frank Cichocki, Jeffrey S Miller, Geoffrey T Hart, Aaron J Johnson, Stephen C Jameson, Sara E Hamilton
Cerebral malaria is a deadly complication of Plasmodium infection and involves blood brain barrier (BBB) disruption following infiltration of white blood cells. During experimental cerebral malaria (ECM), mice inoculated with Plasmodium berghei ANKA-infected red blood cells develop a fatal CM-like disease caused by CD8+ T cell-mediated pathology. We found that treatment with interleukin-15 complex (IL-15C) prevented ECM, whereas IL-2C treatment had no effect. IL-15C-expanded natural killer (NK) cells were necessary and sufficient for protection against ECM...
March 20, 2018: Immunity
https://www.readbyqxmd.com/read/29624921/a-genetic-variant-in-il-15r%C3%AE-correlates-with-physical-activity-among-european-american-adults
#10
Michael Bruneau, Sean Walsh, Eric Selinsky, Garrett Ash, Theodore J Angelopoulos, Priscilla Clarkson, Paul Gordon, Niall Moyna, Paul Visich, Robert Zoeller, Paul Thompson, Heather Gordish-Dressman, Eric Hoffman, Joseph Devaney, Linda S Pescatello
BACKGROUND: Interleukin-15 (IL-15) is a myokine associated with muscle strength, possibly by attenuating protein breakdown. A variant in the alpha-receptor (IL-15Rα 1775 A>C, rs2228059) partially modulates the muscle strength and size response to resistance training. We examined if this polymorphism associated with habitual physical activity among European-American adults. METHODS: Men (n = 240, 23.7 ± 0.3 year, body mass index [BMI] 25.3 ± 0.3 kg/m2 ) and women (n = 292, 23...
April 6, 2018: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/29619608/interleukin-15-concentrations-in-follicular-fluid-and-their-effect-on-oocyte-maturation-in-subfertile-women-undergoing-intracytoplasmic-sperm-injection
#11
S Spanou, D Kalogiannis, E Zapanti, M Gazouli, I A Sfontouris, C Siristatidis, George Mastorakos
PURPOSE: To calculate the concentrations of interleukin 15 (IL-15) in follicular fluid (FF) and evaluate their relation with oocyte maturation, follicle size, and patients' body mass index (BMI) and age. METHODS: Follicular fluid specimens were obtained from 56 subfertile women undergoing intracytoplasmic sperm injection (ICSI) during oocyte retrieval for measurement of IL-15 concentrations with ELISA. Wilcoxon's test and Pearson's correlation coefficient were used to correlate FF concentrations of IL-15 with follicular size and stage of oocyte maturation, along with patients' BMI and age...
April 4, 2018: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/29616032/astrocytic-interleukin-15-reduces-pathology-of-neuromyelitis-optica-in-mice
#12
Zhiguo Li, Jinrui Han, Honglei Ren, Cun-Gen Ma, Fu-Dong Shi, Qiang Liu, Minshu Li
Astrocyte loss induced by neuromyelitis optica (NMO)-IgG and complement-dependent cytotoxicity (CDC) is the hallmark of NMO pathology. The survival of astrocytes is thought to reflect astrocyte exposure to environmental factors in the CNS and the response of astrocytes to these factors. However, still unclear are how astrocytes respond to NMO-IgG and CDC, and what CNS environmental factors may impact the survival of astrocytes. In a murine model of NMO induced by intracerebral injection of NMO-IgG and human complement, we found dramatic upregulation of IL-15 in astrocytes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29588487/trophoblast-derived-cxcl16-induces-m2-macrophage-polarization-that-in-turn-inactivates-nk-cells-at-the-maternal-fetal-interface
#13
Xiao-Qiu Wang, Wen-Jie Zhou, Xin-Xin Hou, Qiang Fu, Da-Jin Li
Decidual macrophages (dMΦ) are distinct from the conventional macrophages present in other tissues and express M2 macrophage markers, but the molecular mechanisms of formation and the roles of M2 MΦ during pregnancy have not been completely elucidated. The crosstalk between decidual natural killer cells (dNK) and dMΦ plays an important role in the maintenance of maternal-fetal immune tolerance. Here, CXCL16 derived from first-trimester trophoblast cells induces the polarization of human M2 macrophages. The M2 MΦ polarized by CXCL16 exhibit decreased interleukin-15 production, which facilitates the inactivation of NK cells...
March 27, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29582584/dysregulation-of-metabolic-associated-pathways-in-muscle-of-breast-cancer-patients-preclinical-evaluation-of-interleukin-15-targeting-fatigue
#14
Joseph Bohlen, Sarah L McLaughlin, Hannah Hazard-Jenkins, Aniello M Infante, Cortney Montgomery, Mary Davis, Emidio E Pistilli
BACKGROUND: Breast cancer patients report a perception of increased muscle fatigue, which can persist following surgery and standardized therapies. In a clinical experiment, we tested the hypothesis that pathways regulating skeletal muscle fatigue are down-regulated in skeletal muscle of breast cancer patients and that different muscle gene expression patterns exist between breast tumour subtypes. In a preclinical study, we tested the hypothesis that mammary tumour growth in mice induces skeletal muscle fatigue and that overexpression of the cytokine interleukin-15 (IL-15) can attenuate mammary tumour-induced muscle fatigue...
March 26, 2018: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29568329/differential-immunological-profiles-herald-magnetic-resonance-imaging-defined-perioperative-cerebral-infarction
#15
Jonathon P Fanning, Louise E See Hoe, Margaret R Passmore, Adrian G Barnett, Barbara E Rolfe, Jonathan E Millar, Allan J Wesley, Jacky Suen, John F Fraser
Background: The perioperative period is associated with a high risk for human ischaemic stroke. Although inflammatory mechanisms are known to have an important role in cerebral infarction in the nonoperative setting, their role in modulating perioperative risk remains unclear. Methods: In this prospective case-control study, we compared 10 patients (cases) who developed magnetic resonance imaging (MRI) evidence of cerebral infarction following transcatheter aortic valve implantation with 10 patients (controls) who underwent the same procedure without neurological complication...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29552626/neutrophil-hepatic-stellate-cell-interactions-promote-fibrosis-in-experimental-steatohepatitis
#16
Zhou Zhou, Ming-Jiang Xu, Yan Cai, Wei Wang, Joy X Jiang, Zoltan V Varga, Dechun Feng, Pal Pacher, George Kunos, Natalie J Torok, Bin Gao
Background & Aims: Hepatic infiltration of neutrophils is a hallmark of steatohepatitis; however, the role of neutrophils in the progression of steatohepatitis remains unknown. Methods: A clinically relevant mouse model of steatohepatitis induced by high-fat diet (HFD) plus binge ethanol feeding was used. Liver fibrosis was examined. In vitro cell culture was used to analyze the interaction of hepatic stellate cells (HSCs) and neutrophils. Results: HFD plus one binge ethanol (HFD+1B) feeding induced significant hepatic neutrophil infiltration, liver injury, and fibrosis...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29542132/how-do-we-manufacture-clinical-grade-interleukin-15-stimulated-natural-killer-cell-products-for-cancer-treatment
#17
Lucía Fernández, Alejandra Leivas, Jaime Valentín, Adela Escudero, Dolores Corral, Raquel de Paz, Maria Vela, David Bueno, Rebeca Rodríguez, Juan Manuel Torres, Mariana Díaz-Almirón, Eduardo López-Collazo, Joaquin Martinez-Lopez, Antonio Pérez-Martínez
BACKGROUND: Cancer immunotherapy involving natural killer (NK) cells has gained interest. Here we report two methods to obtain interleukin (IL)-15-activated NK cells for clinical use. STUDY DESIGN AND METHODS: IL-15-activated NK cell products were obtained after 1) enrichment from healthy haploidentical donors' peripheral blood mononuclear cells (PBMNCs) collected by nonmobilized apheresis by a two-step magnetic procedure, depletion of CD3+ cells followed by selection of CD56+ cells and ex vivo overnight stimulation with IL-15 (NKIL15); and 2) expansion using the K562-mb15-41BBL cell line (NKAE), from autologous PBMNCs from patients with multiple myeloma or expansion from healthy haploidentical PBMNCs obtained from whole blood using the same previous cell line...
March 14, 2018: Transfusion
https://www.readbyqxmd.com/read/29505551/dietary-factors-and-mucosal-immune-response-in-celiac-disease-patients-having-persistent-symptoms-despite-a-gluten-free-diet
#18
Pilvi Laurikka, Katri Lindfors, Mikko Oittinen, Heini Huhtala, Teea Salmi, Marja-Leena Lähdeaho, Tuire Ilus, Markku Mäki, Katri Kaukinen, Kalle Kurppa
GOALS: The aim of this study was to investigate the role of dietary factors, distinct small-bowel mucosal immune cell types, and epithelial integrity in the perpetuation of gastrointestinal symptoms in treated celiac disease patients. BACKGROUND: For unexplained reasons, many celiac disease patients suffer from persistent symptoms, despite a strict gluten-free diet (GFD) and recovered intestinal mucosa. STUDY: We compared clinical and serological data and mucosal recovery in 22 asymptomatic and 25 symptomatic celiac patients on a long-term GFD...
March 2, 2018: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/29472917/senescent-t-cells-promote-bone-loss-in-rheumatoid-arthritis
#19
Johannes Fessler, Rusmir Husic, Verena Schwetz, Elisabeth Lerchbaum, Felix Aberer, Patrizia Fasching, Anja Ficjan, Barbara Obermayer-Pietsch, Christina Duftner, Winfried Graninger, Martin Helmut Stradner, Christian Dejaco
Objective: T-cells are critical players in the pathogenesis of osteoporosis in patients with rheumatoid arthritis (RA). Premature senescence of lymphocytes including the accumulation of senescent CD4+ T-cells is a hallmark feature of RA. Whether T-cell senescence is associated with bone loss in RA patients is elusive so far. Methods: This includes a prospective study of consecutive patients with RA ( n  = 107), patients with primary osteopenia/-porosis ( n  = 75), and healthy individuals ( n  = 38)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29402721/optimized-administration-of-hetil-15-expands-lymphocytes-and-minimizes-toxicity-in-rhesus-macaques
#20
Cristina Bergamaschi, Dionysios C Watson, Antonio Valentin, Jenifer Bear, Cody J Peer, William D Figg, Barbara K Felber, George N Pavlakis
The common γ-chain cytokine interleukin-15 (IL-15) plays a significant role in regulating innate and adaptive lymphocyte homeostasis and can stimulate anti-tumor activity of leukocytes. We have previously shown that the circulating IL-15 in the plasma is the heterodimeric form (hetIL-15), produced upon co-expression of IL-15 and IL-15 Receptor alpha (IL-15Rα) polypeptides in the same cell, heterodimerization of the two chains and secretion. We investigated the pharmacokinetic and pharmacodynamic profile and toxicity of purified human hetIL-15 cytokine upon injection in rhesus macaques...
February 2, 2018: Cytokine
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