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https://www.readbyqxmd.com/read/27910963/daratumumab-monoclonal-antibody-therapy-to-treat-multiple-myeloma
#1
C Xia, M Ribeiro, S Scott, S Lonial
Daratumumab (Darzalex[TM]) is a human monoclonal antibody (MAb) that targets CD38; a surface protein highly expressed across multiple myeloma (MM) cells. Preclinical studies have shown daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), apoptosis upon secondary crosslinking and immunomodulatory effects via a decrease in immune suppressive cells. Daratumumab has a favorable toxicity profile and encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide) and stem cell transplant have already failed...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27910950/human-antibody-3e1-targets-the-ha-stem-region-of-h1n1-and-h5n6-influenza-a-viruses
#2
Wenshuai Wang, Xiaoyu Sun, Yanbing Li, Jinpeng Su, Zhiyang Ling, Tianlong Zhang, Fang Wang, Hong Zhang, Hualan Chen, Jianping Ding, Bing Sun
As influenza A viruses remain a major threat to human health worldwide, the discovery of broadly neutralizing monoclonal antibodies that recognize conserved epitopes would facilitate the development of antibody-based therapeutic strategies. Here we report that a VH4-4-encoded human mAb named 3E1 could neutralize H1 and H5 subtype viruses in vitro and protect mice against the H1N1 and H5N6 viruses by inhibiting the low pH-induced conformational rearrangement of haemagglutinin (HA), hence blocking membrane fusion...
December 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27909730/a-sensitive-and-specific-indirect-competitive-enzyme%C3%A2-linked-immunosorbent-assay-for-the-detection-of-icariin
#3
Jinjun Cheng, Yue Zhang, Shuchen Liu, Baoping Qu, Meiling Zhang, Xiaoman Liu, Yan Zhao, Huihua Qu
In the present study, a novel monoclonal antibody (MAb) specific for icariin (ICA) was prepared and characterized. A hybridoma‑secreting MAb against icariin was produced by fusing splenocytes immunized with an ICA‑bovine serum albumin conjugate with a hypoxanthine‑aminopterin‑thymidine‑sensitive mouse myeloma SP2/0 cell line. The antibody showed high specificity for ICA with almost no cross‑reactivity against the majority of structurally‑related chemicals. Subsequently, an indirect competitive enzyme‑linked immunosorbent assay (ELISA) for ICA was established and characterized...
November 30, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27909235/a-simple-and-sensitive-high-content-assay-for-the-characterization-of-antiproliferative-therapeutic-antibodies
#4
Andreas Stengl, David Hörl, Heinrich Leonhardt, Jonas Helma
Monoclonal antibodies (mAbs) have become a central class of therapeutic agents in particular as antiproliferative compounds. Their often complex modes of action require sensitive assays during early, functional characterization. Current cell-based proliferation assays often detect metabolites that are indicative of metabolic activity but do not directly account for cell proliferation. Measuring DNA replication by incorporation of base analogues such as 5-bromo-2'-deoxyuridine (BrdU) fills this analytical gap but was previously restricted to bulk effect characterization in enzyme-linked immunosorbent assay formats...
December 1, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27908288/granulocyte-macrophage-colony-stimulating-factor-receptor-%C3%AE-expression-and-its-targeting-in-antigen-induced-arthritis-and-inflammation
#5
Andrew D Cook, Cynthia Louis, Matthew J Robinson, Reem Saleh, Matthew A Sleeman, John A Hamilton
BACKGROUND: Blockade of granulocyte macrophage colony-stimulating factor (GM-CSF) and its receptor (GM-CSFRα) is being successfully tested in trials in rheumatoid arthritis (RA) with clinical results equivalent to those found with neutralization of the current therapeutic targets, TNF and IL-6. To explore further the role of GM-CSF as a pro-inflammatory cytokine, we examined the effect of anti-GM-CSFRα neutralization on myeloid cell populations in antigen-driven arthritis and inflammation models and also compared its effect with that of anti-TNF and anti-IL-6...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27907150/molecular-characterization-of-two-monoclonal-antibodies-against-the-same-epitope-on-b-cell-receptor-associated-protein-31
#6
Won-Tae Kim, Saemina Shin, Hyo Jeong Hwang, Min Kyu Kim, Han-Sung Jung, Hwangseo Park, Chun Jeih Ryu
Previously, we showed that B-cell receptor associated protein 31 (BAP31), an endoplasmic reticulum (ER) membrane chaperone, is also expressed on the cell surface by two monoclonal antibodies (MAbs) 297-D4 and 144-A8. Both MAbs recognize the same linear epitope on the C-terminal domain of BAP31, although they were independently established. Here, flow cytometric analysis showed that 144-A8 had additional binding properties to some cells, as compared to 297-D4. Quantitative antigen binding assays also showed that 144-A8 had higher antigen binding capacity than 297-D4...
2016: PloS One
https://www.readbyqxmd.com/read/27907066/b-cell-based-seamless-engineering-of-antibody-fc-domains
#7
Koji Hashimoto, Kohei Kurosawa, Akiho Murayama, Hidetaka Seo, Kunihiro Ohta
Engineering of monoclonal antibodies (mAbs) enables us to obtain mAbs with additional functions. In particular, modifications in antibody's Fc (fragment, crystallizable) region can provide multiple benefits such as added toxicity by drug conjugation, higher affinity to Fc receptors on immunocytes, or the addition of functional modules. However, the generation of recombinant antibodies requires multiple laborious bioengineering steps. We previously developed a technology that enables rapid in vitro screening and isolation of specific mAb-expressing cells from the libraries constructed with chicken B-cell line DT40 (referred to as the 'ADLib system')...
2016: PloS One
https://www.readbyqxmd.com/read/27904138/cirmtuzumab-inhibits-wnt5a-induced-rac1-activation-in-chronic-lymphocytic-leukemia-treated-with-ibrutinib
#8
J Yu, L Chen, B Cui, C Wu, M Y Choi, Y Chen, L Zhang, L Z Rassenti, G F Widhopf, T J Kipps
Signaling via the B cell receptor (BCR) plays an important role in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). This is underscored by the clinical effectiveness of ibrutinib, an inhibitor of Bruton's tyrosine kinase (BTK) that can block BCR-signaling. However, ibrutinib cannot induce complete responses (CR) or durable remissions without continued therapy, suggesting alternative pathways also contribute to CLL growth/survival that are independent of BCR-signaling. ROR1 is a receptor for Wnt5a, which can promote activation of Rac1 to enhance CLL-cell proliferation and survival...
December 1, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27902904/infection-with-some-infectious-bursal-disease-virus-pathotypes-produces-virus-in-chicken-muscle-tissue-and-the-role-of-humoral-immunity-as-a-mitigation-strategy
#9
Mariana Sá E Silva, Kateri Bertran, Kira Moresco, Daral J Jackwood, David E Swayne
Infectious bursal disease virus (IBDV) causes important economic losses and negatively affects global trade in poultry and poultry products. This study determined the presence of IBDV in primary lymphoid tissues and muscle tissue of infected broilers and the role of vaccination as a mitigation strategy. In the first study, specific-pathogen-free (SPF) broiler chickens were challenged with STC (classical [cIBDV]), Indiana (variant [varIBDV]), rA (very virulent [vvIBDV]), or Ohio (serotype 2, avirulent) IBDV...
December 2016: Avian Diseases
https://www.readbyqxmd.com/read/27902333/plant-produced-anti-dengue-virus-monoclonal-antibodies-exhibit-reduced-antibody-dependent-enhancement-of-infection-activity
#10
Matthew Dent, Jonathan Hurtado, Amber M Paul, Haiyan Sun, Huafang Lai, Ming Yang, Adrian Esqueda, Fengwei Bai, Herta Steinkellner, Qiang Chen
The monoclonal antibody (mAb) E60 has the potential to be a desirable therapeutic molecule since it efficiently neutralizes all four serotypes of dengue virus (DENV). However, mammalian cell-produced E60 exhibits antibody-dependent enhancement of infection (ADE) activity, rendering it inefficacious in vivo and subjects treated animals more susceptible to develop more severe diseases during secondary infection. In this study, we evaluated a plant-based expression system for the production of therapeutically suitable E60...
October 20, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27900626/selection-of-chemically-defined-media-for-cho-cell-fed-batch-culture-processes
#11
Xiao Pan, Mathieu Streefland, Ciska Dalm, René H Wijffels, Dirk E Martens
Two CHO cell clones derived from the same parental CHO(BC®) cell line and producing the same monoclonal antibody (BC-G, a low producing clone; BC-P, a high producing clone) were tested in four basal media in all possible combinations with three feeds (=12 conditions) in fed-batch cultures. Higher amino acid feeding did not always lead to higher mAb production. The two clones showed differences in cell physiology, metabolism and optimal medium-feed combinations. During the phase transitions of all cultures, cell metabolism showed a shift represented by lower specific consumption and production rates, except for the specific glucose consumption rate in cultures fed by Actifeed A/B...
November 29, 2016: Cytotechnology
https://www.readbyqxmd.com/read/27899699/a-smartphone-based-genotyping-method-for-hepatitis-b-virus-at-point-of-care-settings
#12
Huiqin Jiang, Di Wu, Liuwei Song, Quan Yuan, Shengxiang Ge, Xiaoping Min, Ningshao Xia, Shizhi Qian, Xianbo Qiu
We reported a rapid, convenient, and easy-to-use genotyping method for hepatitis B virus (HBV) based on the smartphone at point-of-care (POC) settings. To perform HBV genotyping especially for genotypes A, B, C, and D, a smartphone is used to image and analyze a one-step immunoassay lateral flow strip functionalized with genotype-specific monoclonal antibodies (mAbs) on multiple capture lines. A light-emitting diode (LED) positioned on the top of the lateral flow strip is used to shine the multiple capture lines for excitation...
November 29, 2016: Journal of Laboratory Automation
https://www.readbyqxmd.com/read/27898843/influence-of-protein-nutrition-and-virginiamycin-supplementation-on-feedlot-growth-performance-and-digestive-function-of-calf-fed-holstein-steers
#13
J Salinas-Chavira, A Barreras, A Plascencia, M F Montano, J D Navarrete, N Torrentera, R A Zinn
Two experiments were conducted to examine the influence of protein and virginiamycin (VM) supplementation on feedlot growth performance, digestion, and metabolizable AA (MAA) supply of calf-fed Holstein steers. Growth performance and dietary energetics were evaluated in 120 Holstein steers (127 ± 9 kg). During the initial 112-d feeding period, a steam-flaked corn-based diet was balanced to meet either 100% (MAB) or 87% (UREA) of MAA requirements. Diets were supplemented with or without 22.5 mg/kg VM in a 2 × 2 factorial arrangement...
October 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/27896535/generation-of-gene-edited-birds-in-one-generation-using-sperm-transfection-assisted-gene-editing-stage
#14
Caitlin A Cooper, Arjun Challagulla, Kristie A Jenkins, Terry G Wise, Terri E O'Neil, Kirsten R Morris, Mark L Tizard, Timothy J Doran
Generating transgenic and gene edited mammals involves in vitro manipulation of oocytes or single cell embryos. Due to the comparative inaccessibility of avian oocytes and single cell embryos, novel protocols have been developed to produce transgenic and gene edited birds. While these protocols are relatively efficient, they involve two generation intervals before reaching complete somatic and germline expressing transgenic or gene edited birds. Most of this work has been done with chickens, and many protocols require in vitro culturing of primordial germ cells (PGCs)...
November 28, 2016: Transgenic Research
https://www.readbyqxmd.com/read/27894355/generation-of-mabs-to-foot-and-mouth-disease-virus-serotype-a-and-application-in-a-competitive-elisa-for-serodiagnosis
#15
Ming Yang, Wanhong Xu, Hilary Bittner, Jacquelyn Horsington, Wilna Vosloo, Melissa Goolia, Diana Lusansky, Charles Nfon
BACKGROUND: Foot-and-mouth disease (FMD) is an economically devastating disease that severely limits international trade of animals. Of the seven FMD virus (FMDV) serotypes, serotype A is one of the most widespread cross the world. Currently antibodies to FMDV are detected in animals using the virus neutralization test (VNT) and the enzyme-linked immunosorbent assay (ELISA). The VNT is laborious, time-consuming and reliant on live virus and cell cultures, while ELISA has the advantage of using inactivated antigens and often provides more reproducible results...
November 28, 2016: Virology Journal
https://www.readbyqxmd.com/read/27893815/an-accessory-protease-inhibitor-to-increase-the-yield-and-quality-of-a-tumour-targeting-mab-in-nicotiana-benthamiana-leaves
#16
Philippe V Jutras, Carla Marusic, Chiara Lonoce, Carole Deflers, Marie-Claire Goulet, Eugenio Benvenuto, Dominique Michaud, Marcello Donini
The overall quality of recombinant IgG antibodies in plants is dramatically compromised by host endogenous proteases. Different approaches have been developed to reduce the impact of endogenous proteolysis on IgGs, notably involving site-directed mutagenesis to eliminate protease-susceptible sites or the in situ mitigation of host protease activities to minimize antibody processing in the cell secretory pathway. We here characterized the degradation profile of H10, a human tumour-targeting monoclonal IgG, in leaves of Nicotiana benthamiana also expressing the human serine protease inhibitor α1-antichymotrypsin or the cysteine protease inhibitor tomato cystatin SlCYS8...
2016: PloS One
https://www.readbyqxmd.com/read/27892811/simultaneous-determination-of-glycyrrhizin-and-liquiritin-in-licorice-roots-and-kampo-medicines-by-combination-enzyme-linked-immunosorbent-assay-using-anti-glycyrrhizin-and-anti-liquiritin-monoclonal-antibodies
#17
Shunsuke Fujii, Osamu Morinaga, Takuhiro Uto, Shuichi Nomura, Yukihiro Shoyama
Immunoassay systems using monoclonal antibodies (mAbs) are one of the most useful techniques in the analytical, biochemical, and clinical fields. In this study, a combination enzyme-linked immunosorbent assay (ELISA) using both anti-glycyrrhizin and anti-liquiritin mAbs (anti-GL/Liq mixture mAbs) was developed for quality control of licorice and its products. The combination ELISA demonstrated high sensitivity, reproducibility, and specificity for the total content of GL and Liq by a single assay. The developed ELISA was effective and useful as the first screening method in the selection of high-quality licorice from the Glycyrrhiza species and in confirming the quality of licorice-containing Kampo medicines...
November 28, 2016: Journal of Immunoassay & Immunochemistry
https://www.readbyqxmd.com/read/27892793/physiologically-based-modeling-to-predict-the-clinical-behavior-of-monoclonal-antibodies-directed-against-lymphocyte-antigens
#18
Patrick M Glassman, Joseph P Balthasar
Many clinically approved and investigational monoclonal antibody (mAb)-based therapeutics are directed against proteins located in the systemic circulation, including cytokines, growth factors, lymphocyte proteins, and shed antigens. Interaction between mAb and target may lead to non-linear pharmacokinetics (PK), characterized by rapid, target-mediated elimination. Several groups have reported that determinants of target-mediated elimination could include mAb-target binding, target expression, and target turnover...
November 28, 2016: MAbs
https://www.readbyqxmd.com/read/27890931/a-tlr7-agonist-enhances-the-anti-tumor-efficacy-of-obinutuzumab-in-murine-lymphoma-models-via-nk-cells-and-cd4-t-cells
#19
E J Cheadle, G Lipowska-Bhalla, S J Dovedi, E Fagnano, C Klein, J Honeychurch, T M Illidge
Anti-CD20 mAb such as rituximab have proven highly effective at improving outcome in B-cell malignancies. However, many patients ultimately relapse and become refractory to treatment. The glycoengineered anti-CD20 mAb obinutuzumab was developed to induce enhanced antibody dependent cellular cytotoxicity, antibody dependent phagocytosis and direct cell death and was shown to lead to improved outcomes in a randomized study in B-chronic lymphocytic leukemia (B-CLL). We hypothesized that immune stimulation through TLR7 agonism in combination with obinutuzumab would further enhance lymphoma clearance and the generation of long-term anti-tumor immune responses...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27890509/small-scale-screening-method-for-low-viscosity-antibody-solutions-using-small-angle-x-ray-scattering
#20
Masakazu Fukuda, Atsushi Watanabe, Akira Hayasaka, Masaru Muraoka, Yuji Hori, Tadao Yamazaki, Yoshimi Imaeda, Akiko Koga
In this study, we investigated the concentration range in which self-association starts to form in humanized IgG monoclonal antibody (mAb) solutions. Furthermore, on the basis of the results, we developed a practical method of screening for low-viscosity antibody solutions by using small-angle X-ray scattering (SAXS) measurements utilizing small quantities of samples. With lower-viscosity mAb3, self-association was not detected in the range of 1-80 mg/mL. With higher-viscosity mAb1, on the other hand, self-association was detected in the range of 10-20 mg/mL and was clearly enhanced by a decrease in temperature...
November 24, 2016: European Journal of Pharmaceutics and Biopharmaceutics
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