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https://www.readbyqxmd.com/read/29464892/evaluation-of-differences-between-dual-salt-ph-gradient-elution-and-mono-gradient-elution-using-a-thermodynamic-model-simultaneous-separation-of-six-monoclonal-antibody-charge-and-size-variants-on-preparative-scale-ion-exchange-chromatographic-resin
#1
Yi Feng Lee, Matthias Jöhnck, Christian Frech
The efficiencies of mono gradient elution and dual salt-pH gradient elution for separation of six mAb charge and size variants on a preparative-scale ion exchange chromatographic resin are compared in this study. Results showed that opposite dual salt-pH gradient elution with increasing pH gradient and simultaneously decreasing salt gradient is best suited for the separation of these mAb charge and size variants on Eshmuno® CPX. Besides giving high binding capacity, this type of opposite dual salt-pH gradient also provides better resolved mAb variant peaks and lower conductivity in the elution pools compared to single pH or salt gradients...
February 21, 2018: Biotechnology Progress
https://www.readbyqxmd.com/read/29464066/near-infrared-fluorescence-imaging-of-egfr-expression-in-vivo-using-irdye800cw-nimotuzumab
#2
Wendy Bernhard, Ayman El-Sayed, Kris Barreto, Carolina Gonzalez, Wayne Hill, Angel Casaco Parada, Humphrey Fonge, C Ronald Geyer
Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody that is approved in many countries for the treatment of EGFR-positive cancers. Near infrared (NIR) fluorescent dye-labeled antibodies represent an attractive class of image-guided surgical probes because of their high specificity, tumor uptake, and low dissociation from tumor cells that express the antigen. In this study, we developed a NIR fluorescent dye-labeled nimotuzumab immunoconjugate, IRDye800CW-nimotuzumab, and evaluated in vitro binding with EGFR-positive cells, in vivo tumor uptake by NIR fluorescent imaging, and ex vivo biodistribution...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29449526/raised-serum-levels-of-syndecan-1-cd138-in-a-case-of-acute-idiopathic-systemic-capillary-leak-syndrome-scls-clarkson-s-disease
#3
Ole Wilhelm Bøe, Kjell Sveen, Magne Børset, Kirk M Druey
BACKGROUND Systemic capillary leak syndrome (SCLS) (Clarkson's disease) is a rare disorder of unknown etiology, characterized by transient episodes of hypotension, and the microvascular leak of fluids into the peripheral tissues, resulting in edema. Between 80-90% of patients with SCLS have a concomitant monoclonal gammopathy. Although translational in vitro studies have implicated vascular endothelial barrier dysfunction in the etiology of SCLS, the etiology and disease associations in clinical cases remain unknown...
February 16, 2018: American Journal of Case Reports
https://www.readbyqxmd.com/read/29436927/quantitative-analysis-of-glycation-and-its-impact-on-antigen-binding
#4
Jingjie Mo, Renzhe Jin, Qingrong Yan, Izabela Sokolowska, Michael J Lewis, Ping Hu
Glycation has been observed in antibody therapeutics manufactured by the fed-batch fermentation process. It not only increases the heterogeneity of antibodies, but also potentially affects product safety and efficacy. In this study, non-glycated and glycated fractions enriched from a monoclonal antibody (mAb1) as well as glucose-stressed mAb1 were characterized using a variety of biochemical, biophysical and biological assays to determine the effects of glycation on the structure and function of mAb1. Glycation was detected at multiple lysine residues and reduced the antigen binding activity of mAb1...
February 13, 2018: MAbs
https://www.readbyqxmd.com/read/29428991/development-of-orthogonal-nistmab-size-heterogeneity-control-methods
#5
Abigail Turner, Katharina Yandrofski, Srivalli Telikepalli, Jason King, Alan Heckert, James Filliben, Dean Ripple, John E Schiel
The NISTmAb is a monoclonal antibody Reference Material from the National Institute of Standards and Technology; it is a class-representative IgG1κ intended to serve as a pre-competitive platform for harmonization and technology development in the biopharmaceutical industry. The publication series of which this paper is a part describes NIST's overall control strategy to ensure NISTmAb quality and availability over its lifecycle. In this paper, the development of a control strategy for monitoring NISTmAb size heterogeneity is described...
February 10, 2018: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29411091/development-of-an-lc-ms-ms-peptide-mapping-protocol-for-the-nistmab
#6
Trina Mouchahoir, John E Schiel
Peptide mapping is a component of the analytical toolbox used within the biopharmaceutical industry to aid in the identity confirmation of a protein therapeutic and to monitor degradative events such as oxidation or deamidation. These methods offer the advantage of providing site-specific information regarding post-translational and chemical modifications that may arise during production, processing or storage. A number of such variations may also be induced by the sample preparation methods themselves which may confound the ability to accurately evaluate the true modification levels...
February 7, 2018: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29386839/intensely-pruritic-papules-and-plaques-in-waldenstrom-s-macroglobulinemia
#7
Solam Lee, Noo Ri Lee, Sung Jay Choe, Beom Jun Kim, Minseob Eom, Eung Ho Choi
Waldenstrom's macroglobulinemia (WM) is lymphoplasmacytoid malignancy that affects B lymphocytes. Cutaneous involvement of WM is rare, but various cutaneous manifestations have been reported. These findings are due to various pathological processes including direct invasion of tumor cells into the skin, deposition of paraproteins, hyperviscosity syndrome, and cryoglobulinemia. A 64-year-old man presented with a 10-day history of pruritic erythematous papules and plaques on his trunk and elbows. The clinical features were suspicious for eczematous dermatitis...
February 2018: Annals of Dermatology
https://www.readbyqxmd.com/read/29384915/longitudinal-extensive-transverse-myelitis-with-an-abnormal-uflc-ratio-in-a-pediatric-patient-case-report-and-literature-review
#8
REVIEW
Po-Chang Hsu, Shyi-Jou Chen
RATIONALE: The serum and urine-free light chain (sFLC/uFLC) ratios of kappa (κ) to lambda (λ) serve as biomarkers for plasma cell disorders, especially multiple myeloma. However, to our best knowledge, the ratios have not been appropriately assessed for acute transverse myelitis (ATM). PATIENT CONCERNS: We present a 12-year-old boy who had sudden onset low back pain following paralysis of his 4 extremities and disturbance consciousness. Magnetic resonance imaging (MRI) of the brain and spine indicated diffuse hyperintensity in T2-weighted images from the cervical spinal cord to the conus medullaris...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29382470/diagnostic-implications-of-enumerating-and-reporting-beta-fraction-s-for-the-detection-of-beta-migrating-monoclonal-immunoglobulins-in-serum-protein-electrophoresis
#9
Chan Pak Cheung, Bonny Lem-Ragosnig, Jialun Chen
BACKGROUND: Modern serum protein electrophoresis (SPE) resolves serum proteins in 6 major fractions, splitting beta (B) into beta1 (B1) and beta2 (B2). Beta-migrating monoclonal immunoglobulins (B-MC) commonly integrate into normal-looking peak shape(s) but may increase the fraction value, forming the basis for reflex testing. The objectives of this study were (1) to ascertain the value of beta fraction(s) reporting, and (2) to compare the diagnostic performance between different beta-flagging approaches, particularly ↑B versus ↑B1 and/or ↑B2...
January 27, 2018: Clinical Biochemistry
https://www.readbyqxmd.com/read/29378642/anti-%C3%AE-sheet-conformation-monoclonal-antibody-reduces-tau-and-a%C3%AE-oligomer-pathology-in-an-alzheimer-s-disease-model
#10
Fernando Goñi, Mitchell Martá-Ariza, Krystal Herline, Daniel Peyser, Allal Boutajangout, Pankaj Mehta, Eleanor Drummond, Frances Prelli, Thomas Wisniewski
BACKGROUND: Oligomeric forms of amyloid-β (Aβ) and tau are increasing being recognized as key toxins in the pathogenesis of Alzheimer's disease (AD). METHODS: We developed a novel monoclonal antibody (mAb), GW-23B7, that recognizes β-sheet secondary structure on pathological oligomers of neurodegenerative diseases. RESULTS: The pentameric immunoglobulin M kappa chain (IgMκp) we developed specifically distinguishes intra- and extracellular pathology in human AD brains...
January 29, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29371780/cinderella-in-serum-protein-electrophoresis
#11
Srinivas Narasimhachar Chakravarthy, Satish Ramanathan, Smitha Menon, Vijayakumar Valappil, Mathivanan Durairaj, Jayarani Arokia
Paraproteinemia is characterised by clonal proliferation of plasma cells. A common laboratory finding in paraproteinemia being a monoclonal peak in serum protein electrophoresis (M band). But there are factors which produce a peak similar to M spike in serum protein electrophoresis and these factors are known as pseudoparaproteins. This case report discusses a rare cause of pseudo M spike in a known case of autoimmune hemolytic anaemia due to administration of drug-Rituximab, a monoclonal antibody by itself...
January 2018: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/29353350/clinical-pharmacokinetics-and-pharmacodynamics-of-evolocumab-a-pcsk9-inhibitor
#12
REVIEW
Sreeneeranj Kasichayanula, Anita Grover, Maurice G Emery, Megan A Gibbs, Ransi Somaratne, Scott M Wasserman, John P Gibbs
Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases plasma low-density lipoprotein cholesterol (LDL-C) by decreasing expression of the LDL receptor on hepatic cells. Evolocumab is a human monoclonal immunoglobulin G2 that binds specifically to human PCSK9 to reduce LDL-C. Evolocumab exhibits nonlinear kinetics as a result of binding to PCSK9. Elimination is predominantly through saturable binding to PCSK9 at lower concentrations and a nonsaturable proteolytic pathway at higher concentrations. The effective half-life of evolocumab is 11-17 days...
January 20, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29322349/development-of-a-chemically-defined-platform-fed-batch-culture-media-for-monoclonal-antibody-producing-cho-cell-lines-with-optimized-choline-content
#13
Shinobu Kuwae, Ichiko Miyakawa, Tomohiro Doi
A chemically defined platform basal medium and feed media were developed using a single Chinese hamster ovary (CHO) cell line that produces a monoclonal antibody (mAb). Cell line A, which showed a peak viable cell density of 5.9 × 106 cells/mL and a final mAb titer of 0.5 g/L in batch culture, was selected for the platform media development. Stoichiometrically balanced feed media were developed using glucose as an indicator of cell metabolism to determine the feed rates of all other nutrients. A fed-batch culture of cell line A using the platform fed-batch medium yielded a 6...
January 11, 2018: Cytotechnology
https://www.readbyqxmd.com/read/29315494/isotype-dependent-on-column-non-reversible-aggregation-of-monoclonal-antibodies
#14
Monika Farys, Daniel Gibson, Alan Lewis, Will Lewis, Richard Kucia-Tran
Monoclonal antibodies of the IgG2 and IgG4 isotype were found to exhibit an increased propensity for displaying two-peak elution profiles during cation exchange chromatography. In some cases, this two-peak elution profile also resulted in the formation of non-reversible mAb aggregates. Comparison of IgG1, IgG2 and IgG4 molecules with the same variable region reveals that the two-peak behaviour is predominantly mediated by the constant region and most likely the lower CH1, hinge and upper CH2 regions of the mAb...
January 8, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29312544/efficacy-and-safety-of-dupilumab-for-the-treatment-of-moderate-to-severe-atopic-dermatitis-in-adults
#15
Xinghua Xu, Yi Zheng, Xin Zhang, Yanling He, Chengxin Li
Objective: Atopic dermatitis is a chronic, relapsing inflammatory skin disease characterized by intense pruritus, excoriations and limited therapies. Dupilumab, a monoclonal antibody against interleukin-4 receptor alpha, is a promising new treatment option for atopic dermatitis. We sought to systematically summarize the efficacy, safety, and influence on quality of life of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults. Results: A total of 7 RCTs containing 2705 subjects were identified...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29258904/identification-of-t-cell-receptor-expression-in-ebv-positive-neoplastic-cells-in-extranodal-nk-t-cell-lymphoma-nasal-type-and-comparison-with-t-cell-receptor-gene-rearrangement-by-biomed-2-assay
#16
Takuya Takayama, Sohyun Shin, SoYoung Kang, Suk Jin Kim, Won Seog Kim, Young Hyeh Ko
The cellular lineage of extranodal NK/T-cell lymphoma, nasal-type (ENKTL) is determined by expression of T-cell receptor (TR) or TR gene rearrangement. In ENKTL, from TR immunohistochemistry it may often be difficult to decide whether TR-positive cells are tumor cells or not, especially when TR is expressed in a subset of tumor cells. To analyze TR expression pattern and TR rearrangement in T-lineage ENKTL, we performed double immunofluorescence staining for Epstein-Barr virus-encoded small RNAs (EBER) /T-cell receptor (TCR) βF1 and CD56/TCR βF1 in 12 cases of ENKTL that showed TCR βF1 expression in immunohistochemistry...
December 16, 2017: Human Pathology
https://www.readbyqxmd.com/read/29241656/adipose-derived-stem-cells-decrease-pain-in-a-rat-model-of-oxaliplatin-induced-neuropathy-role-of-vegf-a-modulation
#17
Lorenzo Di Cesare Mannelli, Barbara Tenci, Laura Micheli, Alessia Vona, Francesca Corti, Matteo Zanardelli, Andrea Lapucci, Ann Maria Clemente, Paola Failli, Carla Ghelardini
Oxaliplatin therapy of colorectal cancer induces a dose-dependent neuropathic syndrome in 50% of patients. Pharmacological treatments may offer limited relief; scientific efforts are needed for new therapeutic approaches. Therefore we evaluated in a preclinical setting the pain relieving properties of mesenchymal stem cells and its secretome. Rat adipose stem cells (rASCs) were administered in a rat model of oxaliplatin-induced neuropathy. A single intravenous injection of rASCs reduced oxaliplatin-dependent mechanical hypersensitivity to noxious and non-noxious stimuli taking effect 1 h after administration, peaking 6 h thereafter and lasting 5 days...
December 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29239276/radiolabeled-anti-adenosine-triphosphate-synthase-monoclonal-antibody-as-a-theragnostic-agent-targeting-angiogenesis
#18
Bok-Nam Park, Su Jin Lee, Jung Hyun Roh, Kyung-Han Lee, Young-Sil An, Joon-Kee Yoon
INTRODUCTION: The potential of a radioiodine-labeled, anti-adenosine triphosphate synthase monoclonal antibody (ATPS mAb) as a theragnostic agent for simultaneous cancer imaging and treatment was evaluated. METHODS: Adenosine triphosphate synthase monoclonal antibody was labeled with radioiodine, then radiotracer uptake was measured in 6 different cancer cell lines. In vivo biodistribution was evaluated 24 and 48 hours after intravenous injection of 125I-ATPS mAb into MKN-45 tumor-bearing mice (n = 3)...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/29233743/a-phase-ii-trial-of-rituximab-combined-with-pegfilgrastim-in-patients-with-indolent-b-cell-non-hodgkin-lymphoma
#19
Pallawi Torka, Priyank Patel, Wei Tan, Gregory Wilding, Seema A Bhat, Myron S Czuczman, Kelvin P Lee, George Deeb, Vishala Neppalli, Cory Mavis, Paul Wallace, Francisco J Hernandez-Ilizaliturri
BACKGROUND: To explore the role of augmenting neutrophil function in B-cell lymphoma, we conducted a phase II study evaluating the safety and clinical efficacy of pegfilgrastim and rituximab in low-grade CD20+ B-cell non-Hodgkin lymphoma (B-NHL). PATIENTS AND METHODS: Twenty patients with indolent B-NHL were treated with rituximab (375 mg/m2) every other week for 4 doses, followed by every 2 months for 4 additional doses. Pegfilgrastim was administered subcutaneously 3 days before each dose of rituximab...
January 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29217318/ghrh-plus-arginine-and-arginine-administration-evokes-the-same-ratio-of-gh-isoforms-levels-in-young-patients-with-prader-willi-syndrome
#20
Antonello E Rigamonti, Antonino Crinò, Sarah Bocchini, Alessio Convertino, Martin Bidlingmaier, Michael Haenelt, Sofia Tamini, Silvano G Cella, Graziano Grugni, Alessandro Sartorio
Human GH is present in pituitary and circulation as several isoforms, the prevalent being 22kDa- and 20kDa-GH. Recently, we have demonstrated the preservation of a normal balance in GH isoforms after GH releasing hormone (GHRH) plus arginine (ARG) administration in adult patients with Prader-Willi syndrome (PWS), one of the most common causes of syndromic obesity, often associated with GH deficiency (GHD). Aim of the present study was to measure circulating levels of 22kDa- and 20kDa-GH in young PWS patients (n=24; F/M: 10/14; genotype UPD/DEL/met+: 11/11/2; age: 10...
November 27, 2017: Growth Hormone & IGF Research
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