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Human Monoclonal antibodies

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https://www.readbyqxmd.com/read/29786141/an-inhibitory-antibody-targeting-carbonic-anhydrase-xii-abrogates-chemoresistance-and-significantly-reduces-lung-metastases-in-an-orthotopic-breast-cancer-model-in-vivo
#1
Bettina von Neubeck, Gabor Gondi, Chiara Riganti, Chenchen Pan, Arnaldo Parra Damas, Hagen Scherb, Ali Ertürk, Reinhard Zeidler
Carbonic Anhydrase XII (CAXII) is a membrane-tethered ectoenzyme involved in intracellular pH regulation and overexpressed across various types of human cancer. Because CAXII inhibition shows antitumour activity in vitro, it is thought that the enzyme is mandatory for maximum tumour growth, above all under hypoxic conditions. Recently, it has been shown that CAXII is co-expressed along with the P-glycoprotein (P-GP) on many tumour cells and that both proteins physically interact. Of interest, blocking CAXII activity also decreases P-GP activity in cancer cells both in vitro and in vivo...
May 22, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29785730/evidence-of-australian-bat-lyssavirus-infection-in-diverse-australian-bat-taxa
#2
Hume Ernest Field
Historically, Australia was considered free of rabies and rabieslike viruses. Thus, the identification of Australian bat lyssavirus (ABLV) in 1996 in a debilitated bat found by a member of the public precipitated both public health consternation and a revision of lyssavirus taxonomy. Subsequent observational studies sought to elaborate the occurrence and frequency of ABLV infection in Australian bats. This paper describes the taxonomic diversity of bat species showing evidence of ABLV infection to better inform public health considerations...
May 21, 2018: Zoonoses and Public Health
https://www.readbyqxmd.com/read/29784859/igg-responses-to-the-plasmodium-falciparum-antigen-var2csa-in-colombia-are-restricted-to-pregnancy-and-are-not-induced-by-exposure-to-p-vivax
#3
Mary Lopez-Perez, Mads Delbo Larsen, Rafael Bayarri-Olmos, Paulina Ampomah, Liz Stevenson, Myriam Arévalo-Herrera, Sócrates Herrera, Lars Hviid
Clinical immunity to malaria is associated with acquisition of IgG specific for members of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family of clonally variant antigens on the surface of infected erythrocytes (IEs). The VAR2CSA subtype of PfEMP1 mediates IE binding in the placenta. VAR2CSA-specific IgG is normally acquired only after exposure to placental parasites. However, it was recently reported that men and children from Colombia often have high levels of functional VAR2CSA-specific IgG...
May 21, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29784015/induction-of-multiple-myeloma-cancer-stem-cell-apoptosis-using-conjugated-anti-abcg2-antibody-with-epirubicin-loaded-microbubbles
#4
Fangfang Shi, Miao Li, Jing Wang, Di Wu, Meng Pan, Mei Guo, Jun Dou
BACKGROUND: Multiple myeloma (MM) currently remains largely incurable. Cancer stem cells (CSCs) are believed to be responsible for drug resistance and eventual relapse. In this study, we exploited a novel agent to evaluate its inhibitory effect on MM CSCs. METHODS: Epirubicin (EPI)-loaded lipid microbubbles (MBs) conjugated with anti-ABCG2 monoclonal antibody (EPI-MBs + mAb) were developed and their effect on MM 138- CD34- CSCs isolated from human MM RPMI 8226 cell line plus ultrasound exposure in vitro and in vivo in a nonobese diabetic/severe combined immunodeficient mouse model were assessed...
May 21, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29782224/efficacy-and-safety-of-dupilumab-in-glucocorticoid-dependent-severe-asthma
#5
Klaus F Rabe, Parameswaran Nair, Guy Brusselle, Jorge F Maspero, Mario Castro, Lawrence Sher, Hongjie Zhu, Jennifer D Hamilton, Brian N Swanson, Asif Khan, Jingdong Chao, Heribert Staudinger, Gianluca Pirozzi, Christian Antoni, Nikhil Amin, Marcella Ruddy, Bolanle Akinlade, Neil M H Graham, Neil Stahl, George D Yancopoulos, Ariel Teper
Background Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. Its effectiveness in reducing oral glucocorticoid use in patients with severe asthma while maintaining asthma control is unknown. Methods We randomly assigned 210 patients with oral glucocorticoid-treated asthma to receive add-on dupilumab (at a dose of 300 mg) or placebo every 2 weeks for 24 weeks. After a glucocorticoid dose-adjustment period before randomization, glucocorticoid doses were adjusted in a downward trend from week 4 to week 20 and then maintained at a stable dose for 4 weeks...
May 21, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29782217/dupilumab-efficacy-and-safety-in-moderate-to-severe-uncontrolled-asthma
#6
Mario Castro, Jonathan Corren, Ian D Pavord, Jorge Maspero, Sally Wenzel, Klaus F Rabe, William W Busse, Linda Ford, Lawrence Sher, J Mark FitzGerald, Constance Katelaris, Yuji Tohda, Bingzhi Zhang, Heribert Staudinger, Gianluca Pirozzi, Nikhil Amin, Marcella Ruddy, Bolanle Akinlade, Asif Khan, Jingdong Chao, Renata Martincova, Neil M H Graham, Jennifer D Hamilton, Brian N Swanson, Neil Stahl, George D Yancopoulos, Ariel Teper
Background Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma. Methods We randomly assigned 1902 patients 12 years of age or older with uncontrolled asthma in a 2:2:1:1 ratio to receive add-on subcutaneous dupilumab at a dose of 200 or 300 mg every 2 weeks or matched-volume placebos for 52 weeks. The primary end points were the annualized rate of severe asthma exacerbations and the absolute change from baseline to week 12 in the forced expiratory volume in 1 second (FEV1 ) before bronchodilator use in the overall trial population...
May 21, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29782009/construction-of-synthetic-phage-displayed-fab-library-with-tailored-diversity
#7
Ganggang Huang, Zhenwei Zhong, Shane Miersch, Sachdev S Sidhu, Shin-Chen Hou, Donghui Wu
Demand for monoclonal antibodies (mAbs) in basic research and medicine is increasing yearly. Hybridoma technology has been the dominant method for mAb development since its first report in 1975. As an alternative technology, phage display methods for mAb development are increasingly attractive since Humira, the first phage-derived antibody and one of the best-selling mAbs, was approved for clinical treatment of rheumatoid arthritis in 2002. As a non-animal based mAb development technology, phage display bypasses antigen immunogenicity, humanization, and animal maintenance that are required from traditional hybridoma technology based antibody development...
May 1, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29779330/-tolerance-and-pharmacodynamics-phase-%C3%A2-clinical-trial-study-of-chimeric-anti-cd20-monoclonal-antibody-ibi301-in-chinese-patients-with-cd20-positive-non-hodgkin-s-lymphoma
#8
B Jiang, J Y Qi, M Y Sun, Z J Li, W Liu, L J Liu, F K Zhang, L G Qiu
Objective: To evaluate the tolerance and safety of a human-mouse chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients achieved objective response with CD20(+) B-cell non-Hodgkin's lymphoma (NHL). Methods: Nine patients with CD20(+) B-cell NHL received dose-escalating IBI301 infusions (250 mg/m(2), n =3; 375 mg/m(2), n =3; 500 mg/m(2), n =3, respectively). The data of all patients were collected for safety analyses. The median exposures of 125 mg/m(2), 375 mg/m(2), 500 mg/m(2) dose groups were 243, 690 and 980 mg, respectively...
April 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29778566/lung-squamous-cell-carcinoma-cells-express-non-canonically-glycosylated-igg-that-activates-integrin-fak-signaling
#9
Jingshu Tang, Jingxuan Zhang, Yang Liu, Qinyuan Liao, Jing Huang, Zihan Geng, Weiyan Xu, Zhengzuo Sheng, Gregory Lee, Youhui Zhang, Jinfeng Chen, Liang Zhang, Xiaoyan Qiu
It is increasingly recognized that many human carcinomas express immunoglobulin (Ig) molecules that are distinct from B-cell-derived Ig and play important roles in cancer initiation, progression, and metastasis. However, the molecular mechanisms underlying the functions of cancer-derived Ig remain elusive. Here, we report that lung squamous cell carcinoma (LSCC) cells frequently express high levels of cancer IgG (CIgG) that is specifically recognized by a monoclonal antibody RP215. RP215 recognizes CIgG via a novel epitope that involves an N-glycan modification at a non-consensus site within the CH 1 domain...
May 17, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29777858/cd44-targeted-plga-nanomedicines-for-cancer-chemotherapy
#10
REVIEW
Ankit Saneja, Divya Arora, Robin Kumar, Ravindra Dhar Dubey, Amulya K Panda, Prem N Gupta
In recent years scientific community has drawn a great deal of attention towards understanding the enigma of cluster of differentiation-44 (CD44) in order to deliver therapeutic agents more selectively towards tumor tissues. Moreover, its over-expression in variety of solid tumors has attracted drug delivery researchers to target this receptor with nanomedicines. Conventional nanomedicines based on biodegradable polymers such as poly(lactide-co-glycolide) (PLGA) are often associated with insufficient cellular uptake by cancer cells, due to lack of active targeting moiety on their surface...
May 16, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29775731/targeted-and-controlled-drug-delivery-by-multifunctional-mesoporous-silica-nanoparticles-with-internal-fluorescent-conjugates-and-external-polydopamine-and-graphene-oxide-layers
#11
Anh-Vy Tran, KyuHwan Shim, Thu-Thao Vo Thi, Jeong-Keun Kook, Seong Soo A An, Sang-Wha Lee
This study demonstrated the targeted delivery and controlled release of cisplatin drug molecules from doubly decorated mesoporous silica nanoparticles (MSNs), which were internally grafted with fluorescent conjugates and externally coated with polydopamine (PDA) and graphene oxide (GO) layers. The brush-like internal conjugates conferred fluorescent functionality and high capacity of cisplatin loading into MSNs, as well as contributing to a sustained release of the cisplatin through a porous channel with the assistance of external PDA layer...
May 15, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29775564/the-antibody-rhigm22-facilitates-hippocampal-remyelination-and-ameliorates-memory-deficits-in-the-cuprizone-mouse-model-of-demyelination
#12
Charlene Cui, Jing Wang, Ariana P Mullin, Anthony O Caggiano, Tom J Parry, Raymond W Colburn, Elias Pavlopoulos
Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the CNS. In addition to motor, sensory and visual deficits, MS is also characterized by hippocampal demyelination and memory impairment. We recently demonstrated that a recombinant human-derived monoclonal IgM antibody, which is designated rHIgM22 and currently in clinical development for people with MS, accelerates remyelination of the corpus callosum in the brains of cuprizone-treated mice. Here, we investigated the effects of rHIgM22 in the hippocampus and on hippocampal-dependent learning and memory in the same mouse model of cuprizone-induced demyelination and spontaneous remyelination...
May 15, 2018: Brain Research
https://www.readbyqxmd.com/read/29775289/mass-spectral-detection-of-diethoxyphospho-tyrosine-adducts-on-proteins-from-hek293-cells-using-monoclonal-antibody-depy-for-enrichment
#13
Seda Onder, Lawrence M Schopfer, Ozden Tacal, Thomas A Blake, Rudolph C Johnson, Oksana Lockridge
Chronic illness from exposure to organophosphorus toxicants is hypothesized to involve modification of unknown proteins. Tyrosine in proteins that have no active site serine readily reacts with organophosphorus toxicants. We developed a monoclonal antibody, depY, that specifically recognizes diethoxyphospho-tyrosine in proteins and peptides, independent of the surrounding amino acid sequence. Our goal in the current study was to identify diethoxyphosphorylated proteins in human HEK293 cell lysate treated with chlorpyrifos oxon...
May 18, 2018: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29774057/ocrelizumab-a-new-milestone-in-multiple-sclerosis-therapy
#14
REVIEW
Patricia Mulero, Luciana Midaglia, Xavier Montalban
B cells play a central role in the pathogenesis of multiple sclerosis (MS): they are involved in the activation of pro-inflammatory T cells, secretion of pro-inflammatory cytokines and production of autoantibodies directed against myelin. Hence, the use of B cell-depleting monoclonal antibodies as therapy for autoimmune diseases, including MS, has increased in recent years. Previous results with rituximab, the first therapeutic B cell-depleting chimeric monoclonal antibody that showed efficacy in MS clinical trials, encouraged researchers to evaluate the efficacy of a humanized anti-CD20 antibody, ocrelizumab, in MS...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29772250/development-and-validation-of-a-novel-semi-homogenous-clinical-assay-for-quantitation-of-ranibizumab-in-human-serum
#15
John Lowe, Eric Wakshull, Theresa Shek, Anan Chuntharapai, Rebecca Elliott, Jeriza Rusit, Mauricio Maia
Ranibizumab (Lucentis®), a humanized antigen-binding fragment (Fab) monoclonal antibody that blocks VEGF-A activity is currently approved for the treatment of several retinal degenerative diseases. The assessment of drug pharmacokinetics (PK) is essential for evaluating exposure as it relates to drug safety and efficacy. For drugs administered intravitreally, systemic drug levels during the course of clinical studies are typically 100 to 1000-fold lower than those of similar therapeutics dosed intravenously, posing a significant bioanalytical challenge for PK measurements...
May 14, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29771254/guselkumab-human-monoclonal-antibody-against-interleukin-23-for-moderate-to-severe-psoriasis
#16
D M Paton
Guselkumab is an antibody designed to bind to the p19 subunit of interleukin-23 (IL-23). Detailed studies of affected skin in patients with psoriasis demonstrated that guselkumab induced significant changes in the cellular, cytokine and gene expression profiles of psoriatic lesions accompanied by significant changes in clinical measures of disease activity. The significant clinical response in psoriasis was demonstrated in these studies by significant improvement as reflected in the percentage of patients achieving a Physicians Global Assessment score of 0 or 1, and a 90% or 100% improvement in the Psoriasis Area and Severity Index (PASI 90, PASI 100), as well as changes in quality of life measures...
March 2018: Drugs of Today
https://www.readbyqxmd.com/read/29771137/what-sample-preparation-should-be-chosen-for-targeted-ms-monoclonal-antibody-quantification-in-human-serum
#17
Jérôme Vialaret, Sophie Broutin, Célia Pugnier, Sophie Santelé, Aurore Jaffuel, Alan Barnes, Laurent Tiers, Laurent Pelletier, Sylvain Lehmann, Angelo Paci, Christophe Hirtz
AIM: Monoclonal antibody-based treatment of cancer has been established as one of the most successful therapeutic strategies. MATERIALS & METHODS: In this work, we developed a workflow based on an automated protein-A capture and LC-MS/MS analysis to quantify bevacizumab on patient serum during treatment. This analytical approach was fully validated and compared with a commercially available Monoclonal antibody-based treatment preparation (nanosurface and molecular-orientation limited kit)...
May 17, 2018: Bioanalysis
https://www.readbyqxmd.com/read/29770957/first-in-rat-study-of-human-alzheimer-s-disease-tau-propagation
#18
Tomas Smolek, Santosh Jadhav, Veronika Brezovakova, Veronika Cubinkova, Bernadeta Valachova, Petr Novak, Norbert Zilka
One of the key features of misfolded tau in human neurodegenerative disorders is its propagation from one brain area into many others. In the last decade, in vivo tau spreading has been replicated in several mouse transgenic models expressing mutated human tau as well as in normal non-transgenic mice. In this study, we demonstrate for the first time that insoluble tau isolated from human AD brain induces full-blown neurofibrillary pathology in a sporadic rat model of tauopathy expressing non-mutated truncated tau protein...
May 16, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29769725/mxra8-is-a-receptor-for-multiple-arthritogenic-alphaviruses
#19
Rong Zhang, Arthur S Kim, Julie M Fox, Sharmila Nair, Katherine Basore, William B Klimstra, Rebecca Rimkunas, Rachel H Fong, Hueylie Lin, Subhajit Poddar, James E Crowe, Benjamin J Doranz, Daved H Fremont, Michael S Diamond
Arthritogenic alphaviruses comprise a group of enveloped RNA viruses that are transmitted to humans by mosquitoes and cause debilitating acute and chronic musculoskeletal disease 1 . The host factors required for alphavirus entry remain poorly characterized 2 . Here we use a genome-wide CRISPR-Cas9-based screen to identify the cell adhesion molecule Mxra8 as an entry mediator for multiple emerging arthritogenic alphaviruses, including chikungunya, Ross River, Mayaro and O'nyong nyong viruses. Gene editing of mouse Mxra8 or human MXRA8 resulted in reduced levels of viral infection of cells and, reciprocally, ectopic expression of these genes resulted in increased infection...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29769530/comparison-of-the-genotypic-and-phenotypic-properties-of-hiv-1-standard-subtype-b-and-subtype-b-b-env-molecular-clones-derived-from-infections-in-china
#20
Hui Xie, Jianhui Nie, Qingqing Chen, Weijin Huang, Youchun Wang
Although a number of standardized human immunodeficiency virus 1 (HIV-1) pseudoviruses have been generated to assess neutralizing antibodies, subtype B/B' has not been comprehensively characterized either genotypically or phenotypically. Full-length env genes were isolated from plasma samples derived from B/B'-infected individuals, including former plasma donors and men who had sex with men. The neutralization properties of these pseudoviruses were determined by testing against sCD4, 16 neutralizing monoclonal antibodies and 44 plasma samples, including samples from those infected with the three major prevalent clades in China...
May 16, 2018: Emerging Microbes & Infections
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