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https://www.readbyqxmd.com/read/28336678/neutrophils-regulate-the-lung-inflammatory-response-via-%C3%AE-%C3%AE-t-cell-infiltration-in-an-experimental-mouse-model-of-human-metapneumovirus-infection
#1
Nagarjuna R Cheemarla, Ma Del Rocío Baños-Lara, Shan Naidu, Antonieta Guerrero-Plata
Neutrophils are the most abundant leukocytes in human circulation. They are the first immune cell population recruited to the sites of infection. However, the role of neutrophils to regulate host immune responses during respiratory viral infections is largely unknown. To elucidate the role of neutrophils in respiratory antiviral defense, we used an experimental mouse model of human metapneumovirus (HMPV) infection. HMPV, a member of the Paramyxoviridae family, is a leading respiratory pathogen causing severe symptoms, such as bronchiolitis and pneumonia, in young, elderly, and immunocompromised patients...
March 23, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28336546/barrett-s-metaplasia-develops-from-cellular-reprograming-of-esophageal-squamous-epithelium-due-to-gastroesophageal-reflux
#2
Carlos D Minacapelli, Manisha Bajpai, Xin Geng, Christina L Cheng, Abhishek A Chouthai, Rhonda F Souza, Stuart Jon Spechler, Kiron M Das
OBJECTIVE: Gastroesophageal reflux disease (GERD) clinically predisposes to columnar Barrett's metaplasia (BM) in the distal esophagus. We demonstrate evidence supporting cellular origin of BM from reprograming or trans-commitment of resident normal esophageal squamous (NES) epithelial cells in response to acid and bile exposure using an in vitro cell culture model. DESIGN: The hTERT-immortalized NES cell line, NES-B10T, was exposed 5 min/day to Acid and Bile (A+B) mixture for 30 weeks...
March 23, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28335525/the-history-of-clotting-factor-concentrates-pharmacokinetics
#3
REVIEW
Massimo Morfini
Clotting factor concentrates (CFCs) underwent tremendous modifications during the last forty years. Plasma-derived concentrates made the replacement therapy feasible not only in the hospital but also at patients' home by on-demand or prophylactic regimen. Virucidal methods, implemented soon after hepatitis and AIDS outbreak, and purification by Mabs made the plasma-derived concentrates safer and purer. CFCs were considered equivalent to the other drugs and general rules and methods of pharmacokinetics (PK) were applied to their study...
March 20, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28332900/fc-or-not-fc-that-is-the-question-antibody-fc-receptor-interactions-are-key-to-universal-influenza-vaccine-design
#4
Sinthujan Jegaskanda, Hillary A Vanderven, Adam K Wheatley, Stephen J Kent
A universal vaccine that provides long-lasting protection from both epidemic and pandemic influenza viruses remains the "holy grail" of influenza vaccine research. Though virus neutralization assays are the current benchmark of measuring vaccine effectiveness, it is clear that Fc-receptor functions can drastically improve the effectiveness of antibodies and vaccines in vivo. Antibodies that kill virus-infected cells and/or elicit an antiviral environment, termed antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, provide a link between the innate and adaptive immune response...
March 23, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28332627/cross-neutralizing-anti-hiv-1-human-single-chain-variable-fragments-scfvs-against-cd4-binding-site-and-n332-glycan-identified-from-a-recombinant-phage-library
#5
Lubina Khan, Rajesh Kumar, Ramachandran Thiruvengadam, Hilal Ahmad Parray, Muzamil Ashraf Makhdoomi, Sanjeev Kumar, Heena Aggarwal, Madhav Mohata, Abdul Wahid Hussain, Raksha Das, Raghavan Varadarajan, Jayanta Bhattacharya, Madhu Vajpayee, K G Murugavel, Suniti Solomon, Subrata Sinha, Kalpana Luthra
More than 50% of HIV-1 infection globally is caused by subtype_C viruses. Majority of the broadly neutralizing antibodies (bnAbs) targeting HIV-1 have been isolated from non-subtype_C infected donors. Mapping the epitope specificities of bnAbs provides useful information for vaccine design. Recombinant antibody technology enables generation of a large repertoire of monoclonals with diverse specificities. We constructed a phage recombinant single chain variable fragment (scFv) library with a diversity of 7.8 × 10(8) clones, using a novel strategy of pooling peripheral blood mononuclear cells (PBMCs) of six select HIV-1 chronically infected Indian donors whose plasma antibodies exhibited potent cross neutralization efficiency...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332312/antitumor-activity-of-chlpmab-2-a-human-mouse-chimeric-cancer-specific-antihuman-podoplanin-antibody-via-antibody-dependent-cellular-cytotoxicity
#6
Mika K Kaneko, Shinji Yamada, Takuro Nakamura, Shinji Abe, Yasuhiko Nishioka, Akiko Kunita, Masashi Fukayama, Yuki Fujii, Satoshi Ogasawara, Yukinari Kato
Human podoplanin (hPDPN), a platelet aggregation-inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C-type lectin-like receptor 2 (CLEC-2). The overexpression of hPDPN is involved in invasion and metastasis. Anti-hPDPN monoclonal antibodies (mAbs) such as NZ-1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation-stimulating (PLAG) domain of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-2, using the cancer-specific mAb (CasMab) technology...
March 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28331223/therapeutic-efficacy-and-safety-of-pcsk9-monoclonal-antibodies-on-familial-hypercholesterolemia-and-statin-intolerant-patients-a-meta-analysis-of-15-randomized-controlled-trials
#7
Li Jun Qian, Yao Gao, Yan Mei Zhang, Ming Chu, Jing Yao, Di Xu
Proprotein convertase subtilisin/kexin9 monoclonal antibodies (PCSK9-mAb) have been studied intensively to identify their effect in lowering levels of low density lipoprotein cholesterol (LDL-C). However, the applicable target of PCSK9-mAbs remains inconclusive so far. Therefore, this first meta-analysis was carried out to clarify the therapeutic efficacy and safety of PCSK9-mAbs on the potential patients: familial hypercholesterolemia and statin-intolerant patients. All randomized controlled trials that met the search terms were retrieved in multiple databases...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28329114/pcsk9-monoclonal-antibodies-reverse-the-pro-inflammatory-profile-of-monocytes-in-familial-hypercholesterolaemia
#8
Sophie J Bernelot Moens, Annette E Neele, Jeffrey Kroon, Fleur M van der Valk, Jan Van den Bossche, Marten A Hoeksema, Renate M Hoogeveen, Johan G Schnitzler, Marie T Baccara-Dinet, Garen Manvelian, Menno P J de Winther, Erik S G Stroes
Aims: Migration of monocytes into the arterial wall contributes to arterial inflammation and atherosclerosis progression. Since elevated low-density lipoprotein cholesterol (LDL-C) levels have been associated with activation of plasma monocytes, intensive LDL-C lowering may reverse these pro-inflammatory changes. Using proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) which selectively reduce LDL-C, we studied the impact of LDL-C lowering on monocyte phenotype and function in patients with familial hypercholesterolaemia (FH) not using statins due to statin-associated muscle symptoms...
February 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28327200/a-first-in-human-phase-1-study-of-a-hepcidin-monoclonal-antibody-ly2787106-in-cancer-associated-anemia
#9
Saroj Vadhan-Raj, Rafat Abonour, Jonathan W Goldman, David A Smith, Christopher A Slapak, Robert L Ilaria, Ramon V Tiu, Xuejing Wang, Sophie Callies, Joanne Cox, Jay L Tuttle, Yiu-Keung Lau, Eric J Roeland
BACKGROUND: Hepcidin plays a central role in iron homeostasis and erythropoiesis. Neutralizing hepcidin with a monoclonal antibody (mAb) may prevent ferroportin internalization, restore iron efflux from cells, and allow transferrin-mediated iron transport to the bone marrow. This multicenter, phase 1 study evaluated the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of a fully humanized mAb (LY2787106) with high affinity for hepcidin in cancer patients with anemia...
March 21, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28324750/biological-mechanisms-of-immune-escape-and-implications-for-immunotherapy-in-head-and-neck-squamous-cell-carcinoma
#10
REVIEW
Jennifer D Moy, Jessica M Moskovitz, Robert L Ferris
Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high morbidity and mortality. Despite advances in cytotoxic therapies and surgical techniques, overall survival (OS) has not improved over the past few decades. This emphasises the need for intense investigation into novel therapies with good tumour control and minimal toxicity. Cancer immunotherapy has led this endeavour, attempting to improve tumour recognition and expand immune responses against tumour cells. While various forms of HNSCC immunotherapy are in preclinical trials, the most promising direction thus far has been with monoclonal antibodies (mAbs), targeting growth factor and immune checkpoint receptors...
March 18, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28323873/a-three-monoclonal-antibody-combination-potently-neutralizes-multiple-botulinum-neurotoxin-serotype-f-subtypes
#11
Yongfeng Fan, Consuelo Garcia-Rodriguez, Jianlong Lou, Weihua Wen, Fraser Conrad, Wenwu Zhai, Theresa J Smith, Leonard A Smith, James D Marks
Human botulism is primarily caused by botulinum neurotoxin (BoNT) serotypes A, B and E, with around 1% caused by serotype F (BoNT/F). BoNT/F comprises at least seven different subtypes with the amino acid sequence difference between subtypes as high as 36%. The sequence differences present a significant challenge for generating monoclonal antibodies (mAbs) that can bind, detect and neutralize all BoNT/F subtypes. We used repertoire cloning of immune mouse antibody variable (V) regions and yeast display to generate a panel of 33 lead single chain Fv (scFv) mAbs that bound one or more BoNT/F subtypes with a median equilibrium dissociation constant (KD) of 4...
2017: PloS One
https://www.readbyqxmd.com/read/28322160/an-efficient-transient-expression-system-for-enhancing-generation-of-monoclonal-antibodies-in-293-suspension-cells
#12
Guoquan Zhang, Jie Liu, Wanting Fan, Qianyi Chen, Bin Shi
BACKGROUND: Recombinant monoclonal antibodies (mAbs) are useful in research, diagnosis, and therapy. The increased demands of recombinant mAbs require efficient production systems. A variety of expression vectors have been developed for stable or transient production of mAb in mammalian cells. However, though a few commercial expression systems of mAbs can be listened, the high expense often impedes academia researches. METHODS: In this study, we described the development of a transient mammalian system based on a bicistronic vector, which contains internal ribosome entry site (IRES) and enhancer elements to express IgG1 light chain (LC) and heavy chain (HC) in one transcript...
March 20, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28321273/characterization-of-a-new-monoclonal-anti-glypican-3-antibody-specific-to-the-hepatocellular-carcinoma-cell-line-hepg2
#13
Preeyanat Vongchan, Robert J Linhardt
AIM: To characterize the antigen on HepG2 cell that is specifically recognized by a new monoclonal antibody raised against human liver heparan sulfate proteoglycan (HSPG), clone 1E4-1D9. METHODS: The antigen recognized by mAb 1E4-1D9 was immunoprecipitated and its amino acid sequence was analyzed LC/MS. The transmembrane domain, number of cysteine residues, and glycosylation sites were predicted from these entire sequences. Data from amino acid analysis was aligned with glypican-3 (https://www...
March 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28320832/g-csf-receptor-blockade-ameliorates-arthritic-pain-and-disease
#14
Ming-Chin Lee, James A McCubbin, Anne D Christensen, Daniel P Poole, Pradeep Rajasekhar, TinaMarie Lieu, Nigel W Bunnett, Sonia Garcia-Caraballo, Andelain Erickson, Stuart M Brierley, Reem Saleh, Adrian Achuthan, Andrew J Fleetwood, Robin L Anderson, John A Hamilton, Andrew D Cook
G-CSF or CSF-3, originally defined as a regulator of granulocyte lineage development via its cell surface receptor (G-CSFR), can play a role in inflammation, and hence in many pathologies, due to its effects on mature lineage populations. Given this, and because pain is an extremely important arthritis symptom, the efficacy of an anti-G-CSFR mAb for arthritic pain and disease was compared with that of a neutrophil-depleting mAb, anti-Ly6G, in both adaptive and innate immune-mediated murine models. Pain and disease were ameliorated in Ag-induced arthritis, zymosan-induced arthritis, and methylated BSA/IL-1 arthritis by both prophylactic and therapeutic anti-G-CSFR mAb treatment, whereas only prophylactic anti-Ly6G mAb treatment was effective...
March 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28319650/-monoclonal-antibodies-in-the-treatment-of-ms-emergence-of-b-cell-targeted-therapies
#15
REVIEW
Ai-Lan Nguyen, Melissa Gresle, Tessa Marshall, Helmut Butzkueven, Judith Field
Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS, and one of the most common causes of disability in young adults. Over the last decade, new disease modifying therapies have rapidly emerged, including monoclonal antibodies (mAbs) that have provided highly targeted therapies with superior efficacy compared to platform therapies. In particular, monoclonal antibodies directed against CD20-positive B cells have shown remarkable results in recent clinical trials, and renewed interest in the mechanism of B-cell depleting therapies to ameliorate relapse activity and progression in MS...
March 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28319473/precision-medicine-in-asthma-the-role-of-bronchial-thermoplasty
#16
Amber J Oberle, Praveen Mathur
PURPOSE OF REVIEW: The inflammatory makeup of severe asthma is heterogeneous. Identification of the predominant cellular endotype via biomarkers can aid in the selection of more advanced therapies. This review is clinically focused on how to use these biomarkers to help select between biologic agents and/or bronchial thermoplasty. RECENT FINDINGS: Several Th2 biomarkers exist for the detection of eosinophilic disease; however, the best biomarker for clinical practice is debatable depending upon local resources...
March 17, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28317992/synthetic-glycoconjugates-characterize-the-fine-specificity-of-brucella-a-and-m-monoclonal-antibodies
#17
Satadru Sekhar Mandal, N Vijaya Ganesh, Joanna M Sadowska, David R Bundle
The dominant cell wall antigen of Brucella bacteria is the O-polysaccharide component of the smooth lipopolysaccharide. Infection by various Brucella biovars causes abortions and infertility in a wide range of domestic and wild animals and debilitating disease in humans. Diagnosis relies on the detection of antibodies to the A and M antigens expressed in the O-polysaccharide. This molecule is a homopolymer of the rare monosaccharide, 4-formamido-4,6-dideoxy-d-mannopyranose (Rha4NFo). The A epitope is created by a uniform α1,2 linked internal polymeric sequence capped by a distinct tetrasaccharide sequence defining the M antigen...
March 20, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28317872/preclinical-evaluation-of-the-efficacy-pharmacokinetics-and-immunogenicity-of-js-001-a-programmed-cell-death-protein-1-pd-1-monoclonal-antibody
#18
Jie Fu, Fang Wang, Li-Hou Dong, Jing Zhang, Cheng-Lian Deng, Xue-Li Wang, Xin-Yao Xie, Jing Zhang, Ruo-Xian Deng, Li-Bo Zhang, Hai Wu, Hui Feng, Bo Chen, Hai-Feng Song
JS-001 is the first monoclonal antibody (mAb) against programmed cell death protein-1 (PD-1) approved by the China Food and Drug Administration (CFDA) into the clinical trails. To date, however, no pre-clinical pharmacological and pharmacokinetic (PK) data are available. In this study, we investigated the efficacy of JS-001 and conducted a preclinical PK study, including the monitoring of anti-drug antibodies (ADAs). We found that JS-001 specifically bound to PD-1 antigen with an EC50 of 21 nmol/L, and competently blocked the binding of PD-1 antigen to PD-L1 and PD-L2 with IC50 of 3...
March 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28316603/dose-dependent-induction-of-an-idiotypic-cascade-by-anti-glycosaminoglycan-monoclonal-antibody-in-apoe-mice-association-with-atheroprotection
#19
Roger Sarduy, Victor Brito, Adriana Castillo, Yosdel Soto, Tania Griñán, Sylvie Marleau, Ana María Vázquez
Atherosclerosis, the underlying pathology of most cardiovascular diseases, is triggered by the retention of apolipoprotein B (apoB)-containing lipoproteins in the arterial wall through electrostatic interactions with glycosaminoglycan (GAG) side chains of proteoglycans. Previously, we reported the antiatherogenic properties of the chimeric monoclonal antibody (mAb) chP3R99-LALA, which binds sulfated GAGs, inhibits low-density lipoprotein (LDL)-chondroitin sulfate (CS) association, and abrogates LDL oxidation and foam cell formation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28315359/antibodies-and-associates-partners-in-targeted-drug-delivery
#20
REVIEW
Patrick J Kennedy, Carla Oliveira, Pedro L Granja, Bruno Sarmento
Monoclonal antibodies (mAbs) are well established in the clinic due to their specificity and affinity to a diverse array of biochemical targets. More recently, mAbs are being exploited as targeting agents in modern drug delivery systems, aiming to bypass normal host tissue and to accumulate a therapeutic agent to a specific tissue or cell for enhanced pharmacology. At sizes ranging from ~10-100nm, antibody-based bioconjugates have opened up a whole new realm of clinical possibilities with several platforms emerging on the market...
March 14, 2017: Pharmacology & Therapeutics
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