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Monoclonal peak

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https://www.readbyqxmd.com/read/28088282/conjugation-site-analysis-of-antibody-drug-conjugates-adcs-by-signature-ion-fingerprinting-and-normalized-area-quantitation-approach-using-nano-liquid-chromatography-coupled-to-high-resolution-mass-spectrometry
#1
Hua Sang, Gaoyuan Lu, Yazhong Liu, Qiyue Hu, Weifeng Xing, Dongbing Cui, Fang Zhou, Jingwei Zhang, Haiping Hao, Guangji Wang, Hui Ye
Trastuzumab-MCC-DM1 (T-DM1) is an antibody-drug conjugate (ADC) that consists of a monoclonal antibody (mAb) trastuzumab non-cleavably linked to a cytotoxic drug DM1. During production, the DM1 agents were conjugated to the lysine residues of the mAb in a non-specific manner, yielding a heterogeneous mixture of ADC molecules that differ with respect to both the number and the conjugation sites of DM1 per mAb molecule. Since drug conjugation sites of ADC can significantly impact properties such as stability and pharmacokinetic behaviors, a rapid and reliable approach for conjugation site analysis of ADCs is highly demanded...
February 22, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28087106/charge-variant-analysis-of-proposed-biosimilar-to-trastuzumab
#2
Pravinkumar Dakshinamurthy, Pavithra Mukunda, Bhargav Prasad Kodaganti, Bharath Ravindra Shenoy, Bairavabalakumar Natarajan, Amol Maliwalave, Vivek Halan, Sathyabalan Murugesan, Sunit Maity
Trastuzumab is a humanized monoclonal antibody (mAb) employed for the treatment of HER2 Positive Breast Cancer. A HER2 overexpressing tumor cell binds to Trastuzumab and attracts immune cells which lead to induction of Antibody Dependent Cellular Cytotoxicity (ADCC) by binding to Fc receptors (CD16a or FcγRIIIa) on an effector cell, such as natural killer (NK) cells. The most commonly expressed receptor on NK cell is CD16a which binds to the Fc portion of Trastuzumab. The ligand-independent HER2-HER3 dimerization is the most potent stimulator of downstream pathways for regulation of cell growth and survival...
January 10, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28061947/b-lymphocytes-forming-follicle-like-structures-in-the-lung-tissue-of-tuberculosis-infected-mice-dynamics-phenotypes-and-functional-activity
#3
Irina Linge, Alexander Dyatlov, Elena Kondratieva, Vadim Avdienko, Alexander Apt, Tatiana Kondratieva
During tuberculosis (TB) infection, B cells form follicles in close vicinity of lung granuloma. We assessed the dynamics of follicle formation, surface phenotypes and functional activity of lung B cells during TB course in genetically susceptible mice. The follicles appeared early post infection and peaked at weeks 7-8. Lung B cells resembled classical B2 cells (CD19(+)IgMloIgD(hi)CD1d(-)CD21/35(int)CD5(-)CD11b(-)CD43(-)), but differed from them by the absence of B2 marker CD23. Lung B-cells constitutively expressed MHC II molecules, presented mycobacterial antigens to immune CD4(+) T-cells and produced high amounts of IL-6 and IL-11, but no classical type 1 (TNF-α, IFN-γ), or anti-inflammatory (IL-10, TGF-β) cytokines...
January 2017: Tuberculosis
https://www.readbyqxmd.com/read/28042070/fatigue-during-and-after-breast-cancer-therapy-a-prospective-study
#4
Kristin V Reinertsen, Olav Engebraaten, Jon H Loge, Milada Cvancarova, Bjørn Naume, Erik Wist, Hege Edvardsen, Elisabeth Wille, Trine Bjøro, Cecilie E Kiserud
CONTEXT: Chronic fatigue (CF) in breast cancer (BC) survivors is multifactorial and may be caused by immune activation triggered by BC or its treatment. In the NeoAva study, BC patients received neoadjuvant chemotherapy (FEC100→taxane) +/-bevacizumab, a monoclonal antibody with fatigue as a potential side effect. OBJECTIVES: To examine fatigue levels and prevalence of CF before and during chemotherapy and at follow-up (FU), and their associations with C-reactive protein (CRP) and clinical variables...
December 29, 2016: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28008632/in-capillary-approach-to-eliminate-sds-interferences-in-antibody-analysis-by-capillary-electrophoresis-coupled-to-mass-spectrometry
#5
Laura Sánchez-Hernández, Cristina Montealegre, Steffen Kiessig, Bernd Moritz, Christian Neusüß
Capillary electrophoresis is an important technique for the characterization of monoclonal antibodies (mAbs), especially in the pharmaceutical context. However, identification is difficult as upscaling and hyphenation of used methods directly to mass spectrometry is often not possible due to separation medium components that are incompatible with MS detection. Here a CE-MS method for the analysis of mAbs is presented analyzing SDS-complexed samples. To obtain narrow and intensive peaks of SDS-treated antibodies, an in-capillary strategy was developed based on the co-injection of positively charged surfactants and methanol as organic solvent...
December 23, 2016: Electrophoresis
https://www.readbyqxmd.com/read/28000101/remarkable-pharmacokinetics-of-monoclonal-antibodies-a-quest-for-an-explanation
#6
Joannes A A Reijers, Matthijs Moerland, Jacobus Burggraaf
Monoclonal antibodies (MAbs) usually display slow and limited distribution with combined linear and non-linear elimination mechanisms. While studying individual pharmacokinetic profiles, it was noticed that MAb plasma concentration can vary abruptly over time, with one or more increases after the time to maximum plasma concentration when theoretically the concentration should only decline. This article summarizes the frequency of these additional peaks and assesses whether normal intra-subject and assay variability can explain the observations...
December 20, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27997765/intracellular-cho-cell-metabolite-profiling-reveals-steady-state-dependent-metabolic-fingerprints-in-perfusion-culture
#7
Daniel J Karst, Robert Steinhoff, Marie R G Kopp, Elisa Serra, Miroslav Soos, Renato Zenobi, Massimo Morbidelli
Perfusion cell culture processes allow the steady-state culture of mammalian cells at high viable cell density, which is beneficial for overall product yields and homogeneity of product quality in the manufacturing of therapeutic proteins. In this study, the extent of metabolic steady state and the change of the metabolite profile between different steady states of an industrial Chinese hamster ovary (CHO) cell line producing a monoclonal antibody (mAb) was investigated in stirred tank perfusion bioreactors...
December 20, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27994435/pkr-promotes-choroidal-neovascularization-via-upregulating-the-pi3k-akt-signaling-pathway-in-vegf-expression
#8
Manhui Zhu, Xiaojuan Liu, Shengcun Wang, Jin Miao, Liucheng Wu, Xiaowei Yang, Ying Wang, Lihua Kang, Wendie Li, Chen Cui, Hui Chen, Aimin Sang
PURPOSE: The aim of this study was to investigate the functions of dsRNA-activated protein kinase (PKR) in choroidal neovascularization (CNV) and related signaling pathways in the production of vascular endothelial growth factor (VEGF). METHODS: A chemical hypoxia model of in vitro RF/6A cells, a rhesus choroid-retinal endothelial cell line, was established by adding cobalt chloride (CoCl2) to the culture medium. PKR, phosphophosphatidylinositol 3-kinase (p-PI3K), phosphoprotein kinase B (p-Akt), and VEGF protein levels in RF/6A cells were detected with western blotting...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27934109/in-vivo-biotransformation-of-the-fusion-protein-tetranectin-apolipoprotein-a1-analyzed-by-ligand-binding-mass-spectrometry-combined-with-quantitation-by-elisa
#9
Manfred Zell, Christophe Husser, Roland F Staack, Gregor Jordan, Wolfgang F Richter, Simone Schadt, Axel Pähler
The in vivo biotransformation of a novel fusion protein tetranectin/apolipoprotein A1 (TN-ApoA1) was investigated by ligand-binding mass spectrometry (LB-MS) in support of enzyme-linked immunosorbent assays (ELISA). The main focus was on catabolites formed by proteolysis of the fusion protein in rabbit following intravenous administration of lipidated TN-ApoA1. The drug and its catabolites were isolated from rabbit plasma by immunocapture with a monoclonal antibody (mAb) binding to the fusion region of TN-ApoA1...
December 6, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27902473/rituximab-conjugated-doxorubicin-loaded-microbubbles-as-a-theranostic-modality-in-b-cell-lymphoma
#10
Shoubing Zhou, Xiu Zhang, Cailian Wang
This study evaluated rituximab-conjugated, doxorubicin-loaded microbubbles (RDMs) in combination with ultrasound as molecular imaging agents for early diagnosis of B cell lymphomas, and as a targeted drug delivery system. Rituximab, a monoclonal CD20 antibody, was attached to the surfaces of doxorubicin-loaded microbubbles. RDM binding to B cell lymphoma cells was assessed using immunofluorescence. The cytotoxic effects of RDMs in combination with ultrasound (RDMs+US) were evaluated in vitro in CD20+ and CD20- cell lines, and its antitumor activities were assessed in Raji (CD20+) and Jurkat (CD20-) lymphoma cell-grafted mice...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27887763/composite-lymphoma-with-diffuse-large-b-cell-lymphoma-and-classical-hodgkin-lymphoma-components-a-case-report-and-review-of-the-literature
#11
Gaurav Goyal, Austin Huy Nguyen, Kayla Kendric, Gabriel C Caponetti
Composite lymphoma (CL) is an infrequently diagnosed entity in which two or more distinct types of lymphomas occur synchronously in the same organ or anatomical site. Most commonly, CLs are composed of two non-Hodgkin B-cell lymphomas. We present a case of a composite lymphoma with diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS) and classical Hodgkin lymphoma (CHL) components involving the terminal ileum, colon and pericolic lymph nodes. Immunohistochemical evaluation for determination of cell of origin of the DLBCL-NOS component indicated a germinal center B-cell subtype...
December 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27886550/v%C3%AE-1-%C3%AE-%C3%AE-t-early-cardiac-infiltrated-innate-population-dominantly-producing-il-4-protect-mice-against-cvb3-myocarditis-by-modulating-ifn%C3%AE-t-response
#12
Fangfang Wan, Kepeng Yan, Dan Xu, Qian Qian, Hui Liu, Min Li, Wei Xu
Viral myocarditis (VMC) is an inflammation of the myocardium closely associated with Coxsackievirus B3 (CVB3) infection. Vγ1(+)γδT cells, one of early cardiac infiltrated innate population, were reported to protect CVB3 myocarditis while the precise mechanism not fully addressed. To explore cytokine profiles and kinetics of Vγ1(+)γδT and mechanism of protection against VMC, flow cytometry was conducted on cardiac Vγ1 cells in C57BL/6 mice following CVB3 infection. The level of cardiac inflammation, transthoracic echocardiography and viral replication were evaluated after monoclonal antibody depletion of Vγ1γδT...
January 2017: Molecular Immunology
https://www.readbyqxmd.com/read/27885684/interference-free-mass-spectrometric-detection-of-capillary-isoelectric-focused-proteins-including-charge-variants-of-a-model-monoclonal-antibody
#13
Jens Hühner, Kevin Jooß, Christian Neusüß
CIEF represents an elegant technique especially for the separation of structural similar analytes, whereas MS is a state-of-the-art instrumentation for the identification and characterization of biomolecules. The combination of both techniques can be realized by hyphenating CIEF with CZE-ESI-MS applying a mechanical valve. During the CZE step, the remaining ESI-interfering components of the CIEF electrolyte are separated from the analytes prior to MS detection. In this work, a multiple heart-cut approach is presented expanding our previous single heart-cut concept resulting in a dramatical reduction of analysis time...
November 25, 2016: Electrophoresis
https://www.readbyqxmd.com/read/27875559/efficacy-and-safety-of-anti-interleukin-5-therapy-in-patients-with-asthma-a-systematic-review-and-meta-analysis
#14
Fa-Ping Wang, Ting Liu, Zhu Lan, Su-Yun Li, Hui Mao
BACKGROUND: Recent trials have assessed the efficacy and safety of novel monoclonal antibodies such as reslizumab and benralizumab. However, the overall efficacy and safety anti-interleukin (IL) 5 treatment in asthma have not been thoroughly assessed. METHODS: Randomized controlled trials (RCTs) of anti-IL-5 treatment on patients with asthma published up to October 2016 in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) that reported pulmonary function, quality of life scores, asthmatic exacerbation rate, blood and sputum eosinophil counts, short-acting β-agonist (SABA) rescue use, and adverse events were included...
2016: PloS One
https://www.readbyqxmd.com/read/27852589/effects-of-the-p-selectin-antagonist-inclacumab-on-myocardial-damage-after-percutaneous-coronary-intervention-according-to-timing-of-infusion-insights-from-the-select-acs-trial
#15
Barbara E Stähli, Catherine Gebhard, Valérie Duchatelle, Daniel Cournoyer, Thibaut Petroni, Jean-François Tanguay, Stephen Robb, Jessica Mann, Marie-Claude Guertin, R Scott Wright, Philippe L L'Allier, Jean-Claude Tardif
BACKGROUND: The Effects of the P-Selectin Antagonist Inclacumab on Myocardial Damage After Percutaneous Coronary Intervention for Non-ST-Segment Elevation Myocardial Infarction (SELECT-ACS) trial suggested beneficial effects of inclacumab, a monoclonal antibody directed against P-selectin, on periprocedural myocardial damage. This study evaluated the effect of inclacumab on myocardial damage according to varying time intervals between study drug infusion and percutaneous coronary intervention (PCI)...
November 16, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27824651/infliximab-selectively-modulates-the-circulating-blood-monocyte-repertoire-in-crohn-s-disease
#16
Stephanie M Slevin, Michael Conall Dennedy, Eanna P Connaughton, Andreia Ribeiro, Rhodri Ceredig, Matthew D Griffin, Laurence J Egan
BACKGROUND: Infliximab (IFX), an anti-tumour necrosis factor alpha (TNFα) monoclonal antibody, provides clinical benefits in treating Crohn's disease (CD) but its mechanisms of action are not fully elucidated. This study investigated blood monocyte repertoires and the acute effects of IFX infusion on monocyte subset phenotype and function in IFX-treated patients with CD. METHODS: Monocytes and monocyte subsets were enumerated and phenotypically characterized by multicolor flow cytometry in freshly isolated blood from healthy controls (n = 21) and patients with CD treated with (IFX, n = 24) and without (non-IFX, n = 20) IFX...
December 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27802880/surface-induced-three-peak-elution-behavior-of-a-monoclonal-antibody-during-cation-exchange-chromatography
#17
Jing Guo, Arch D Creasy, Gregory Barker, Giorgio Carta
A monoclonal antibody exhibits a two- or three-peak elution behavior when loaded on the CEX resin POROS XS and eluted with a salt gradient. Two peaks are observed without a hold step while a third more strongly retained peak becomes noticeable with a hold time as low as 10min. As the hold time is increased further, the first peak gradually disappears, the second peak initially increases and then decreases, and the third peak continuously increases. Dynamic light scattering shows that the third peak contains significant levels of aggregates formed in the column...
October 26, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/27795368/safety-tolerability-and-pharmacokinetics-of-medi4893-an-investigational-extended-half-life-anti-staphylococcus-aureus-alpha-toxin-human-monoclonal-antibody-in-healthy-adults
#18
Xiang-Qing Yu, Gabriel J Robbie, Yuling Wu, Mark T Esser, Kathryn Jensen, Howard I Schwartz, Terramika Bellamy, Martha Hernandez-Illas, Hasan S Jafri
MEDI4893 is an investigational immunoglobulin G1(κ) monoclonal antibody that specifically binds to and neutralizes alpha-toxin, a key Staphylococcus aureus virulence factor. A triple-amino-acid substitution, M252Y/S254T/T256E, was engineered into the MEDI4893 Fc region to extend its serum half-life. A phase 1, double-blind, dose escalation study was designed to evaluate the safety, tolerability, pharmacokinetics, anti-alpha-toxin-neutralizing activity, and antidrug antibody (ADA) response of MEDI4893 following a single intravenous infusion in healthy adults 18 to 65 years of age...
January 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27794039/visualization-of-dna-g-quadruplexes-in-herpes-simplex-virus-1-infected-cells
#19
Sara Artusi, Rosalba Perrone, Sara Lago, Paolo Raffa, Enzo Di Iorio, Giorgio Palù, Sara N Richter
We have previously shown that clusters of guanine quadruplex (G4) structures can form in the human herpes simplex-1 (HSV-1) genome. Here we used immunofluorescence and immune-electron microscopy with a G4-specific monoclonal antibody to visualize G4 structures in HSV-1 infected cells. We found that G4 formation and localization within the cells was virus cycle dependent: viral G4s peaked at the time of viral DNA replication in the cell nucleus, moved to the nuclear membrane at the time of virus nuclear egress and were later found in HSV-1 immature virions released from the cell nucleus...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27754462/toxicity-and-growth-assessments-of-three-thermophilic-benthic-dinoflagellates-ostreopsis-cf-ovata-prorocentrum-lima-and-coolia-monotis-developing-in-the-southern-mediterranean-basin
#20
Hela Ben-Gharbia, Ons Kéfi-Daly Yahia, Zouher Amzil, Nicolas Chomérat, Eric Abadie, Estelle Masseret, Manoella Sibat, Habiba Zmerli Triki, Habiba Nouri, Mohamed Laabir
Harmful benthic dinoflagellates, usually developing in tropical areas, are expanding to temperate ecosystems facing water warming. Reports on harmful benthic species are particularly scarce in the Southern Mediterranean Sea. For the first time, three thermophilic benthic dinoflagellates (Ostreopsis cf. ovata, Prorocentrum lima and Coolia monotis) were isolated from Bizerte Bay (Tunisia, Mediterranean) and monoclonal cultures established. The ribotyping confirmed the morphological identification of the three species...
October 15, 2016: Toxins
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