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https://www.readbyqxmd.com/read/28716814/potency-matched-dual-cytokine-antibody-fusion-proteins-for-cancer-therapy
#1
Roberto De Luca, Alex Soltermann, Francesca Pretto, Catherine Pemberton-Ross, Giovanni Pellegrini, Sarah Wulhfard, Dario Neri
A novel biopharmaceutical, consisting of the F8 monoclonal antibody (specific to a splice isoform of fibronectin) simultaneously fused to both tumor necrosis factor and interleukin-2, was found to react with the majority of solid tumors and hematological malignancies in mouse and man, but not with healthy adult tissues. The product selectively localized to neoplastic lesions in vivo, as evidenced by quantitative biodistribution studies using radioiodinated protein preparations. When the potency of the cytokine payloads was matched by a single-point mutation, the resulting fusion protein (IL2-F8-TNF(mut)) eradicated soft-tissue sarcomas in immunocompetent mice, which did not respond to individual antibody-cytokine fusion proteins or by standard doxorubicin treatment...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28713365/what-s-normal-immune-profiling-of-human-milk-from-healthy-women-living-in-different-geographical-and-socioeconomic-settings
#2
Lorena Ruiz, Irene Espinosa-Martos, Cristina García-Carral, Susana Manzano, Michelle K McGuire, Courtney L Meehan, Mark A McGuire, Janet E Williams, James Foster, Daniel W Sellen, Elizabeth W Kamau-Mbuthia, Egidioh W Kamundia, Samwel Mbugua, Sophie E Moore, Linda J Kvist, Gloria E Otoo, Kimberly A Lackey, Katherine Flores, Rossina G Pareja, Lars Bode, Juan M Rodríguez
Human milk provides a very wide range of nutrients and bioactive components, including immune factors, human milk oligosaccharides, and a commensal microbiota. These factors are essential for interconnected processes including immunity programming and the development of a normal infant gastrointestinal microbiome. Newborn immune protection mostly relies on maternal immune factors provided through milk. However, studies dealing with an in-depth profiling of the different immune compounds present in human milk and with the assessment of their natural variation in healthy women from different populations are scarce...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28702029/inflammation-related-gene-polymorphisms-associated-with-primary-immune-thrombocytopenia
#3
Ju Li, Sai Ma, Linlin Shao, Chunhong Ma, Chengjiang Gao, Xiao-Hui Zhang, Ming Hou, Jun Peng
Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by a reduced platelet count and an increased risk of bleeding. Although immense research has improved our understanding of ITP, the pathogenesis remains unclear. Here, we investigated the involvement of 25 single-nucleotide polymorphisms (SNPs) of the inflammation-related genes, including CD24, CD226, FCRL3, IL2, IRF5, ITGAM, NLRP3, CARD8, PTPN22, SH2B2, STAT4, TNFAIP3, and TRAF1, in the pathogenesis and treatment response of ITP...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28686482/outer-membrane-vesicles-blebbing-contributes-to-b-vulgatus-mpk-mediated-immune-response-silencing
#4
Jan Kevin Maerz, Alex Steimle, Anna Lange, Annika Bender, Birgit Fehrenbacher, Julia-Stefanie Frick
The Gram negative intestinal symbiont Bacteroides vulgatus mpk is able to prevent from induction of colonic inflammation in Rag1(-/-) mice and promotes immune balance in Il2(-/-) mice. These inflammation-silencing effects are associated with B. vulgatus mpk-mediated induction of semi-mature dendritic cells, especially in the colonic lamina propria (cLP). However the beneficial interaction of bacteria with host immune cells is limited due to the existence of a large mucus layer covering the intestinal epithelium...
July 7, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28686294/nfat-regulated-cytokine-gene-expression-during-tacrolimus-therapy-early-after-renal-transplantation
#5
Sara Bremer, Nils T Vethe, Morten Skauby, Margrete Kasbo, Elisabet D Johansson, Karsten Midtvedt, Stein Bergan
AIMS: Despite pharmacokinetic monitoring of calcineurin inhibitors, the long-term outcome after transplantation (Tx) is still hampered by the side effects of these drugs. The aim of this study was to characterize the nuclear factor of activated T cells (NFAT)-regulated gene expression as a potential pharmacodynamic biomarker for further individualization of tacrolimus (Tac) therapy. METHODS: In 29 renal allograft recipients samples were drawn once pre-Tx, and before and 1...
July 7, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28679475/cik-as-therapeutic-agents-against-tumors
#6
REVIEW
M Introna
Cytokine Induced Killer (CIK) cells are ex vivo expanded and activated T lymphocytes obtained by sequential incubation of Peripheral Blood Mononuclear cells (PBMNC) with Interferon γ (IFNG), anti CD3 monoclonal antibody OKT3 and IL2. These cells, while retaining few characteristics of the Effector memory T cells subpopulation, acquired during culture CD56 expression, as well as non specific, Natural Killer like, anti tumoral cytotoxicity. CIK cells from human are equivalent to expanded NKT cells in mouse...
July 2, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28678791/modeling-the-receptor-pharmacology-pharmacokinetics-and-pharmacodynamics-of-nktr-214-a-kinetically-controlled-interleukin-2-il2-receptor-agonist-for-cancer-immunotherapy
#7
Deborah Charych, Samira Khalili, Vidula Dixit, Peter Kirk, Thomas Chang, John Langowski, Werner Rubas, Stephen K Doberstein, Michael Eldon, Ute Hoch, Jonathan Zalevsky
Cytokines are potent immune modulating agents but are not ideal medicines in their natural form due to their short half-life and pleiotropic systemic effects. NKTR-214 is a clinical-stage biologic that comprises interleukin-2 (IL2) protein bound by multiple releasable polyethylene glycol (PEG) chains. In this highly PEG-bound form, the IL2 is inactive; therefore, NKTR-214 is a biologic prodrug. When administered in vivo, the PEG chains slowly release, creating a cascade of increasingly active IL2 protein conjugates bound by fewer PEG chains...
2017: PloS One
https://www.readbyqxmd.com/read/28660319/the-clinical-efficacy-of-first-generation-carcinoembryonic-antigen-ceacam5-specific-car-t-cells-is-limited-by-poor-persistence-and-transient-pre-conditioning-dependent-respiratory-toxicity
#8
Fiona C Thistlethwaite, David E Gilham, Ryan D Guest, Dominic G Rothwell, Manon Pillai, Deborah J Burt, Andrea J Byatte, Natalia Kirillova, Juan W Valle, Surinder K Sharma, Kerry A Chester, Nigel B Westwood, Sarah E R Halford, Stephen Nabarro, Susan Wan, Eric Austin, Robert E Hawkins
The primary aim of this clinical trial was to determine the feasibility of delivering first-generation CAR T cell therapy to patients with advanced, CEACAM5(+) malignancy. Secondary aims were to assess clinical efficacy, immune effector function and optimal dose of CAR T cells. Three cohorts of patients received increasing doses of CEACAM5(+)-specific CAR T cells after fludarabine pre-conditioning plus systemic IL2 support post T cell infusion. Patients in cohort 4 received increased intensity pre-conditioning (cyclophosphamide and fludarabine), systemic IL2 support and CAR T cells...
June 28, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28653038/interleukins-and-large-domestic-animals-a-bibliometric-analysis
#9
Emmanuelle Moreau, François Meurens
Interleukins have been well described in mice and humans. In large domestic animals the situation is drastically different and there is still a need for further researches aiming at identifying all the homologous interleukins and comparing their functions among species. We performed here a bibliometric analysis of all interleukins described in the literature in various large animal species to identify what is known so far and to underline where there is a need for new studies. Using indicators such as H index but also M quotient, A index, G index, GH ratio, and HG index we ranked 39 interleukins identified so far in bovine, caprine, equine, ovine, and porcine, the main large domestic animals...
June 2017: Heliyon
https://www.readbyqxmd.com/read/28629743/association-study-of-childhood-food-allergy-with-gwas-discovered-loci-of-atopic-dermatitis-and-eosinophilic-esophagitis
#10
Tomomitsu Hirota, Tsuguhisa Nakayama, Sakura Sato, Noriyuki Yanagida, Teruaki Matsui, Shiro Sugiura, Yuri Takaoka, Nobuyuki Hizawa, Shigeharu Fujieda, Akihiko Miyatake, Takashi Sasaki, Masayuki Amagai, Satoru Doi, Komei Ito, Motohiro Ebisawa, Mayumi Tamari
We found associations between FA and 14 GWAS-identified loci of AD and EoE: C11orf30/LRRC32, TMEM232/SLC25A46, TNFRSF6B/ZGPAT, OVOL1, KIF3A/IL13, GLB1, CCDC80, ZNF365, OR10A3/NLRP10, IL2/IL21, CLEC16A/DEXI, ZNF652, TSLP/WDR36 and STAT6. These findings improve our understanding of the complex heterogeneity of FA.
June 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28607106/ubash3a-mediates-risk-for-type-1-diabetes-through-inhibition-of-t-cell-receptor-induced-nf-%C3%AE%C2%BAb-signaling
#11
Yan Ge, Taylor K Paisie, Jeremy R B Newman, Lauren M McIntyre, Patrick Concannon
Although over 40 type 1 diabetes (T1D) risk loci have been mapped in humans, the causative genes and variants for T1D are largely unknown. Here, we investigated a candidate gene in the 21q22.3 risk locus-UBASH3A, which is primarily expressed in T cells where it is thought to play a largely redundant role. Genetic variants in UBASH3A have been shown to be associated with several autoimmune diseases in addition to T1D. However, the molecular mechanism underlying these genetic associations is unresolved. Our study reveals a previously unrecognized role of UBASH3A in human T cells: UBASH3A attenuates the NF-κB signal transduction upon T-cell receptor (TCR) stimulation by specifically suppressing the activation of the IκB kinase complex...
July 2017: Diabetes
https://www.readbyqxmd.com/read/28589963/exposure-to-the-abused-inhalant-toluene-alters-medial-prefrontal-cortex-physiology
#12
Wesley N Wayman, John J Woodward
Inhalants, including toluene, target the addiction neurocircuitry and are often one of the first drugs of abuse tried by adolescents. The medial prefrontal cortex (mPFC) is involved in regulating goal-directed/reward-motivated behaviors and different mPFC sub-regions have been proposed to promote (prelimbic, PRL) or inhibit (infralimbic, IL) these behaviors. While this dichotomy has been studied in the context of other drugs of abuse, it is not known whether toluene exposure differentially affects neurons within PRL and IL regions...
June 7, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28573158/mouse-embryonic-fibroblast-cell-culture-and-stimulation
#13
Lian-Qun Qiu, Wi S Lai, Deborah J Stumpo, Perry J Blackshear
Culture of mouse embryonic fibroblast (MEF) cells represents a powerful system to test gene function due to their easy accessibility, rapid growth rates, and the possibility of a large number of experiments. Fibroblasts are a group of heterogeneous resident cells of mesenchymal origin that have various locations, diverse appearances and distinctive activities. Because of their ubiquitous distribution as tissue cells, these cells are poised to respond to factors released by newly activated innate immune cells, thus becoming a useful tool to study inflammation and immunity...
July 5, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28570278/cxcl13-producing-tfh-cells-link-immune-suppression-and-adaptive-memory-in-human-breast-cancer
#14
Chunyan Gu-Trantien, Edoardo Migliori, Laurence Buisseret, Alexandre de Wind, Sylvain Brohée, Soizic Garaud, Grégory Noël, Vu Luan Dang Chi, Jean-Nicolas Lodewyckx, Céline Naveaux, Hugues Duvillier, Stanislas Goriely, Denis Larsimont, Karen Willard-Gallo
T follicular helper cells (TFH cells) are important regulators of antigen-specific B cell responses. The B cell chemoattractant CXCL13 has recently been linked with TFH cell infiltration and improved survival in human cancer. Although human TFH cells can produce CXCL13, their immune functions are currently unknown. This study presents data from human breast cancer, advocating a role for tumor-infiltrating CXCL13-producing (CXCR5-) TFH cells, here named TFHX13 cells, in promoting local memory B cell differentiation...
June 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/28556984/the-emerging-role-of-anti-cd25-directed-therapies-as-both-immune-modulators-and-targeted-agents-in-cancer
#15
REVIEW
Michael J Flynn, John A Hartley
CD25 (also termed IL2RA) forms one component of the high-affinity heterotrimeric interleukin 2 (IL2) receptor on activated T cells. Its affinity for IL2 and cellular function are tightly regulated and vary in different cell types. The high frequency of CD25 on the surface of many different haematological tumour cells is now well established and, apart from its prognostic significance, CD25 may be present on leukaemic stem cells and enable oncogenic signalling pathways in leukaemic cells. Additionally, high CD25 expression in activated circulating immune cells and Tregs is a factor that has already been exploited by IL2 immunotherapies for treatment of tumours and autoimmune disease...
May 30, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28554143/comparison-of-gene-expression-of-toll-like-receptors-and-cytokines-between-piau-and-commercial-line-landrace%C3%A3-large-white-crossbred-pigs-vaccinated-against-pasteurella-multocida-type-d
#16
Katiene Régia Silva Sousa, André Mauric Frossard Ribeiro, Waleska de Melo Ferreira Dantas, Leandro Licursi de Oliveira, Eliane Gasparino, Simone Eliza Facioni Guimarães
We aimed to compare Toll-like receptors (TLR) and cytokines expression in local Piau breed and a Commercial line (Landrace×Large White crossbred) pigs in response to vaccination against Pasteurella multocida type D. Seronegative gilts for Pasteurella multocida type D and Mycoplasma hyopneumoniae were used, from which peripheral blood mononuclear cells (PBMC) were collected in four time points (T0, T1, T2 and T3; before and after each vaccination dose). For bronchoalveolar lavage fluid cells (BALF), we set groups of vaccinated and unvaccinated animals for both genetic groups...
May 22, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28529323/an-immunogenic-phenotype-in-paternal-antigen-specific-cd8-t-cells-at-embryo-implantation-elicits-later-fetal-loss-in-mice
#17
Lachlan M Moldenhauer, Kerrilyn R Diener, John D Hayball, Sarah A Robertson
Central to pregnancy success is a state of T cell tolerance to paternal antigens, which is initiated at conception. The role and regulation of specific phenotypes of CD8(+) T cells in mediating pregnancy tolerance is not clear. This study aimed to investigate the impact on pregnancy outcome of altering the cytokine environment during maternal CD8(+) T cell priming in early pregnancy. Transgenic Act-mOVA male mice were mated to C57BL/6 (B6) females to generate fetuses expressing ovalbumin (OVA) as a model paternal antigen...
May 22, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28524801/association-of-ugt2b7-ugt1a9-abcg2-and-il23r-polymorphisms-with-rejection-risk-in-kidney-transplant-patients
#18
Heloísa Lizotti Cilião, Rossana Batista Oliveira Camargo-Godoy, Marilesia Ferreira de Souza, Mariana Bisarro Dos Reis, Lorena Iastrenski, Vinicius Daher Alvares Delfino, Silvia Regina Rogatto, Ilce Mara de Syllos Cólus
Despite advances in testing compatibility between donor and recipient, graft rejection remains a current concern. Single-nucleotide polymorphisms (SNPs) that codify altered enzymes of metabolism, drug transport, and the immune system may contribute to graft rejection in transplant patients. This study examined the association between SNPs present in genes of these processes and occurrence of graft rejection episodes in 246 kidney transplant patients, 35% of which were diagnosed with rejection. Genotype-gene expression associations were also assessed...
May 19, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28507940/cord-blood-cells-responses-to-il2-il7-and-il15-cytokines-for-mtor-expression
#19
Anahita Mohammadian, Elahe Naderali, Seyedeh Momeneh Mohammadi, Aliakbar Movasaghpour, Behnaz Valipour, Mohammad Nouri, Hojjatollah Nozad Charoudeh
Purpose: Mammalian target of rapamycin (mTOR)is important in hematopoiesis and affect cell growth,differentiation and survival. Although previous studies were identified the effect of cytokines on the mononuclear cells development however the cytokines effect on mTOR in cord blood mononuclear cells was unclear. The aim of this study was to evaluate mTOR expression in cord blood mononuclear and cord blood stem cells (CD34(+) cells) in culture conditions for lymphoid cell development. Methods: Isolation of The mononuclear cells (MNCs) from umbilical cord blood were done with use of Ficollpaque density gradient...
April 2017: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28507797/il15-induces-a-potent-antitumor-activity-in-nk-cells-isolated-from-malignant-pleural-effusions-and-overcomes-the-inhibitory-effect-of-pleural-fluid
#20
D Croxatto, S Martini, L Chiossone, F Scordamaglia, C F Simonassi, L Moretta, M C Mingari, P Vacca
Natural Killer (NK) cells are capable of recognizing and killing cancer cells and play an important role in tumor immunosurveillance. However, tumor-infiltrating NK cells are frequently impaired in their functional capability. A remarkable exception is represented by NK cells isolated from malignant pleural effusions (PE) that are not anergic and, upon IL2-induced activation, efficiently kill tumor cells. Although IL2 is used in various clinical trials, severe side effects may occur in treated patients. In this study, we investigated whether also other clinical-grade cytokines could induce strong cytotoxicity in NK cells isolated from pleural fluid of patients with primary or metastatic tumors of different origins...
2017: Oncoimmunology
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