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https://www.readbyqxmd.com/read/29454004/identification-and-analysis-of-peanut-specific-t-effector-and-t-regulatory-cells-in-children-allergic-and-tolerant-to-peanut
#1
Katherine A Weissler, Marjohn Rasooly, Tom DiMaggio, Hyejeong Bolan, Daly Cantave, David Martino, Melanie R Neeland, Mimi Lk Tang, Thanh D Dang, Katrina J Allen, Pamela A Frischmeyer-Guerrerio
BACKGROUND: Peanut allergy is potentially life-threatening and generally persists lifelong. Recent data suggests the skin may be an important route of initial sensitization to peanut, while early oral exposure to peanut is protective. In mice, T regulatory cells (Tregs) are central to development of tolerance to food, but their contribution to the pathogenesis of food allergy in humans is less clear. OBJECTIVE: We sought to quantify and phenotype peanut-specific CD4+ T effector (ps-Teff) and ps-Tregs in children with and without peanut allergy or sensitization...
February 14, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29433059/resveratrol-liposomes-and-lipid-nanocarriers-comparison-of-characteristics-and-inducing-browning-of-white-adipocytes
#2
Yujiao Zu, Haley Overby, Guofeng Ren, Zhaoyang Fan, Ling Zhao, Shu Wang
Trans-resveratrol (R) has a potential to increase energy expenditure via inducing browning in white adipose tissue. However, its low levels of aqueous solubility, stability, and poor bioavailability limit its application. We have successfully synthesized biocompatible, and biodegradable R encapsulated lipid nanocarriers (R-nano), and R encapsulated liposomes (R-lipo). The mean particle size of R-nano and R-lipo were 140 nm and 110 nm, respectively, and their polydispersity index values were less than 0...
December 27, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29396470/augmentation-of-cd134-ox40-dependent-nk-anti-tumour-activity-is-dependent-on-antibody-cross-linking
#3
Anna H Turaj, Kerry L Cox, Christine A Penfold, Ruth R French, C Ian Mockridge, Jane E Willoughby, Alison L Tutt, Jordana Griffiths, Peter W M Johnson, Martin J Glennie, Ronald Levy, Mark S Cragg, Sean H Lim
CD134 (OX40) is a member of the tumour necrosis factor receptor superfamily (TNFRSF). It acts as a costimulatory receptor on T cells, but its role on NK cells is poorly understood. CD137, another TNFRSF member has been shown to enhance the anti-tumour activity of NK cells in various malignancies. Here, we examine the expression and function of CD134 on human and mouse NK cells in B-cell lymphoma. CD134 was transiently upregulated upon activation of NK cells in both species. In contrast to CD137, induction of CD134 on human NK cells was dependent on close proximity to, or cell-to-cell contact with, monocytes or T cells...
February 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29327109/a-novel-biologic-platform-elicits-profound-t-cell-costimulatory-activity-and-antitumor-immunity-in-mice
#4
Joseph M Ryan, Payal Mittal, Antoine Menoret, Julia Svedova, Jeffrey S Wasser, Adam J Adler, Anthony T Vella
Combination immunotherapies utilizing complementary modalities that target distinct tumor attributes or immunosuppressive mechanisms, or engage different arms of the antitumor immune response, can elicit greater therapeutic efficacy than the component monotherapies. Increasing the number of agents included in a therapeutic cocktail can further increase efficacy, however, this approach poses numerous challenges for clinical translation. Here, a novel platform to simplify combination immunotherapy by covalently linking immunotherapeutic agonists to the costimulatory receptors CD134 and CD137 into a single heterodimeric drug, "OrthomAb", is shown...
January 11, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29325369/-cd137-signaling-promotes-the-formation-of-plaque-calcification-via-inhibiting-the-fusion-of-autophagy-and-lysosomal-in-apo-e-mice
#5
X Y Li, R Chen, W Zhong, B Li, C Shao, Z Q Wang, J C Yan
Objective: To investigate whether CD137 signaling promoted the formation of atherosclerotic plaque calcification by inhibiting the fusion of autophagosome and lysosome. Methods: (1) In vivo, CD137 agonist antibody and anti-CD137 antibody were used to stimulate and inhibit the CD137 signaling, respectively. Fifteen Apo E(-/-) mice were randomly divided into three groups: control group (intraperitoneal injection of IgG2b 200 µg) , CD137 agonist group (intraperitoneal injection of CD137 agonist antibody 200 µg) , anti-CD137 group (pretreatment with 200 µg anti-CD137 antibody for 24 hours, then injection of CD137 agonist antibody) ...
December 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/29305435/an-immunotherapeutic-cd137-agonist-releases-eomesodermin-from-thpok-repression-in-cd4-t-cells
#6
Payal Mittal, Rebecca Abblett, Joseph M Ryan, Adam T Hagymasi, Archibald Agyekum-Yamoah, Julia Svedova, Steven L Reiner, Marie-Clare St Rose, Matthew P Hanley, Anthony T Vella, Adam J Adler
Agonists to the TNF/TNFR costimulatory receptors CD134 (OX40) and CD137 (4-1BB) elicit antitumor immunity. Dual costimulation with anti-CD134 plus anti-CD137 is particularly potent because it programs cytotoxic potential in CD8+ and CD4+ T cells. Cytotoxicity in dual-costimulated CD4 T cells depends on the T-box transcription factor eomesodermin (Eomes), which we report is induced via a mechanism that does not rely on IL-2, in contrast to CD8+ CTL, but rather depends on the CD8 T cell lineage commitment transcription factor Runx3, which supports Eomes expression in mature CD8+ CTLs...
January 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29301830/activation-of-4-1bb-on-liver-myeloid-cells-triggers-hepatitis-via-an-interleukin-27-dependent-pathway
#7
Todd Bartkowiak, Ashvin R Jaiswal, Casey R Ager, Renee Chin, Chao-Hsien Chen, Pratha Budhani, Midan Ai, Matthew J Reilley, Manu M Sebastian, David S Hong, Michael A Curran
PURPOSE: Agonist antibodies targeting the T cell co-stimulatory receptor 4-1BB (CD137) are among the most effective immunotherapeutic agents across pre-clinical cancer models. In the clinic, however, development of these agents has been hampered by dose-limiting liver toxicity. Lack of knowledge of the mechanisms underlying this toxicity has limited the potential to separate 4-1BB agonist driven tumor immunity from hepatotoxicity. EXPERIMENTAL DESIGN: The capacity of 4-1BB agonist antibodies to induce liver toxicity was investigated in immunocompetent mice, with or without co-administration of checkpoint blockade, via 1) measurement of serum transaminase levels, 2) imaging of liver immune infiltrates, and 3) qualitative and quantitative assessment of liver myeloid and T cells via flow cytometry...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29298689/anti-gd2-4-1bb-chimeric-antigen-receptor-t-cell-therapy-for-the-treatment-of-chinese-melanoma-patients
#8
Jiayi Yu, Xiaowen Wu, Junya Yan, Huan Yu, Longwen Xu, Zhihong Chi, Xinan Sheng, Lu Si, Chuanliang Cui, Jie Dai, Meng Ma, Tianxiao Xu, Yan Kong, Jun Guo
BACKGROUND: Chimeric antigen receptor (CAR)-engineered T cells have demonstrated promising clinical efficacy in patients with B cell lymphoma. However, the application of CAR-T cell therapy in the treatment of other solid tumors has been limited. We incorporated 4-1BB into the anti-GD2 CAR-T cells to test their cytotoxicity in melanoma in vitro and in vivo. Moreover, we reported the expression of ganglioside GD2 in non-Caucasian melanoma populations for the first time, thus providing a basis for future clinical research...
January 3, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29295974/nanoparticle-anchoring-targets-immune-agonists-to-tumors-enabling-anti-cancer-immunity-without-systemic-toxicity
#9
Yuan Zhang, Na Li, Heikyung Suh, Darrell J Irvine
Immunostimulatory agents such as agonistic anti-CD137 and interleukin (IL)-2 generate effective anti-tumor immunity but also elicit serious toxicities, hampering their clinical application. Here we show that combination therapy with anti-CD137 and an IL-2-Fc fusion achieves significant initial anti-tumor activity, but also lethal immunotoxicity deriving from stimulation of circulating leukocytes. To overcome this toxicity, we demonstrate that anchoring IL-2 and anti-CD137 on the surface of liposomes allows these immune agonists to rapidly accumulate in tumors while lowering systemic exposure...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29242193/crystal-structure-of-murine-4-1bb-and-its-interaction-with-4-1bbl-support-a-role-for-galectin-9-in-4-1bb-signaling
#10
Aruna Bitra, Tzanko Doukov, Jing Wang, Gaelle Picarda, Chris A Benedict, Michael Croft, Dirk M Zajonc
4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 4-1BB also can bind to the tandem repeat-type lectin Galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in Galectin-9 (Gal-9) deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. Here, using sulfur-SAD phasing, we determined the crystal structure of m4-1BB to 2.2 Å resolution...
December 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29236301/synergistic-effect-of-carnosine-on-browning-of-adipose-tissue-in-exercised-obese-rats-a-focus-on-circulating-irisin-levels
#11
Mona F Schaalan, Basma K Ramadan, Azza H Abd Elwahab
BACKGROUND: The recent appreciation of the energy burning capacity of brown adipose tissue turns it to an attractive target as anti-obesity therapy. OBJECTIVE: to evaluate the effect of L-carnosine on browning of white adipose tissue in exercised obese rats. METHODS: Sixty adult male Wistar albino rats between 7-8 weeks-old weighing 130-150 g were allocated into six groups;(i) normal control rats fed normal diet; (ii) high fat diet (HFD)-induced obese rats, (iii) normal control rats fed normal diet and injected with L-carnosine (250mg/kg), (iv) HFD-rats injected with L-carnosine (250mg/kg),(v): HFD-rats subjected to exercise training; (vi): HFD- rats subjected to exercise training and L-carnosine together...
December 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29217172/nobiletin-induces-brown-adipocyte-like-phenotype-and-ameliorates-stress-in-3t3-l1-adipocytes
#12
Jameel Lone, Hilal Ahmad Parray, Jong Won Yun
Browning of white adipocytes (beiging) is an attractive therapeutic strategy against obesity and its associated metabolic complications. Nobiletin (NOB) is a polymethoxylated flavone present in Citrus fruits and has been reported to have anti-obesity effects. Here, we report that nobiletin exerts dual modulatory effects on adipocytes via induction of browning in 3T3-L1 white adipocytes and amelioration of stress in adipocytes. Nobiletin-induced beiging was investigated by determining expression levels of beige-specific genes and proteins by RT-PCR and immunoblot analysis, respectively...
December 4, 2017: Biochimie
https://www.readbyqxmd.com/read/29188818/no-evidence-of-white-adipocyte-browning-after-endurance-exercise-training-in-obese-men
#13
T Tsiloulis, A L Carey, J Bayliss, B Canny, R C R Meex, M J Watt
BACKGROUND/OBJECTIVES: The phenomenon of adipocyte 'beiging' involves the conversion of non-classic brown adipocytes to brown-like adipose tissue with thermogenic, fat-burning properties, and this phenomenon has been shown in rodents to slow the progression of obesity-associated metabolic diseases. Rodent studies consistently report adipocyte beiging after endurance exercise training, indicating that increased thermogenic capacity in these adipocytes may underpin the improved health benefits of exercise training...
November 30, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29179214/cetuximab-enhanced-the-cytotoxic-activity-of-immune-cells-during-treatment-of-colorectal-cancer
#14
Lin Wang, Yingfeng Wei, Weijia Fang, Chong Lu, Jianing Chen, Guangying Cui, Hongyan Diao
BACKGROUND/AIMS: Cetuximab is a chimeric IgG1 monoclonal antibody which targets the extracellular domain of epidermal growth factor receptor. This antibody is widely used for colorectal cancer (CRC) treatment but its influence on the immune system is incompletely understood. METHODS: The immune influence of cetuximab therapy in CRC patients was investigated by analyzing peripheral blood mononuclear cells using flow cytometry. We undertook in vitro cytotoxicity and cytokine-profile assays to ascertain the immunomodulatory effect of cetuximab treatment...
November 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29151956/strategies-for-bispecific-single-chain-antibody-in-cancer-immunotherapy
#15
REVIEW
Shu-Juan Zhou, Jia Wei, Shu Su, Fang-Jun Chen, Yu-Dong Qiu, Bao-Rui Liu
Genetic engineering has resulted in more than 50 recombinant bispecific antibody formats over the past two decades. Bispecific scFv antibodies represent a successful and promising immunotherapy platform that retargets cytotoxic T cells to tumor cells, with one scFv directed to tumor-associated antigens and the other to T cells. Based on this antibody construct, strategies for both specific tumor targeting and T cell activation are reviewed here. Three distinct types of tumor antigens are considered to optimize specificity and safety in bispecific scFv based treatment: cancer-testis antigens, neo-antigens and virus-associated antigens...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29133290/cd137-4-1bb-costimulation-modifies-dna-methylation-in-cd8-t-cell-relevant-genes
#16
M Angela Aznar, Sara Labiano, Angel Diaz-Lagares, Carmen Molina, Saray Garasa, Arantza Azpilicueta, Inaki Etxeberria, Alfonso R Sanchez-Paulete, Alan J Korman, Manel Esteller, Juan Sandoval, Ignacio Melero
CD137 (4-1BB) costimulation imprints long-term changes that instruct the ultimate behavior of T cells that have previously experienced CD137 ligation. Epigenetic changes could provide a suitable mechanism for these long-term consequences. Genome-wide DNA-methylation arrays were carried out on human peripheral blood CD8+ T lymphocytes stimulated with agonist monoclonal antibody to CD137, including urelumab, which is in phase I/II clinical trials for cancer immunotherapy. Several genes showed consistent methylation patterns in response to CD137 costimulation, which were confirmed by pyrosequencing in a series of healthy donors...
November 13, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29118009/immunotherapy-targeting-4-1bb-mechanistic-rationale-clinical-results-and-future-strategies
#17
Cariad Chester, Miguel F Sanmamed, Jun Wang, Ignacio Melero
4-1BB (CD137, TNFRSF9) is an inducible costimulatory receptor expressed on activated T and natural killer (NK) cells. 4-1BB ligation on T cells triggers a signaling cascade that results in upregulation of antiapoptotic molecules, cytokine secretion, and enhanced effector function. In dysfunctional T cells that have a decreased cytotoxic capacity, 4-1BB ligation demonstrates a potent ability to restore effector functions. On NK cells, 4-1BB signaling can increase antibody-dependent cell-mediated cytotoxicity...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29114608/4-1bb-cd137-and-radiation-therapy-a-case-report-and-literature-review
#18
Jay C Shiao, Nathan Bowers, Tahseen H Nasti, Faisal Khosa, Mohammad K Khan
No abstract text is available yet for this article.
July 2017: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/29103912/optimization-of-il13r%C3%AE-2-targeted-chimeric-antigen-receptor-t-cells-for-improved-anti-tumor-efficacy-against-glioblastoma
#19
Christine E Brown, Brenda Aguilar, Renate Starr, Xin Yang, Wen-Chung Chang, Lihong Weng, Brenda Chang, Aniee Sarkissian, Alfonso Brito, James F Sanchez, Julie R Ostberg, Massimo D'Apuzzo, Behnam Badie, Michael E Barish, Stephen J Forman
T cell immunotherapy is emerging as a powerful strategy to treat cancer and may improve outcomes for patients with glioblastoma (GBM). We have developed a chimeric antigen receptor (CAR) T cell immunotherapy targeting IL-13 receptor α2 (IL13Rα2) for the treatment of GBM. Here, we describe the optimization of IL13Rα2-targeted CAR T cells, including the design of a 4-1BB (CD137) co-stimulatory CAR (IL13BBζ) and a manufacturing platform using enriched central memory T cells. Utilizing orthotopic human GBM models with patient-derived tumor sphere lines in NSG mice, we found that IL13BBζ-CAR T cells improved anti-tumor activity and T cell persistence as compared to first-generation IL13ζ-CAR CD8(+) T cells that had shown evidence for bioactivity in patients...
October 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29079845/glycolipid-peptide-conjugate-vaccines-enhance-cd8-t-cell-responses-against-human-viral-proteins
#20
M Speir, A Authier-Hall, C R Brooks, K J Farrand, B J Compton, R J Anderson, A Heiser, T L Osmond, C W Tang, J A Berzofsky, M Terabe, G F Painter, I F Hermans, R Weinkove
An important goal of vaccination against viruses and virus-driven cancers is to elicit cytotoxic CD8(+) T cells specific for virus-derived peptides. CD8(+) T cell responses can be enhanced by engaging help from natural killer T (NKT) cells. We have produced synthetic vaccines that induce strong peptide-specific CD8(+) T cell responses in vivo by incorporating an NKT cell-activating glycolipid. Here we examine the effect of a glycolipid-peptide conjugate vaccine incorporating an NKT cell-activating glycolipid linked to an MHC class I-restricted peptide from a viral antigen in human peripheral blood mononuclear cells...
October 27, 2017: Scientific Reports
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