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Human Monoclonal antibodies

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https://www.readbyqxmd.com/read/29334721/efficacy-and-safety-of-tocilizumab-in-korean-patients-with-active-rheumatoid-arthritis
#1
Han Joo Baek, Mie Jin Lim, Won Park, Sung Hwan Park, Seung-Cheol Shim, Dae-Hyun Yoo, Hyun Ah Kim, Soo Kon Lee, Yun Jong Lee, Young Eun Park, Hoon-Suk Cha, Yeong-Wook Song
Background/Aims: To investigate the efficacy and safety of tocilizumab (TCZ) humanized anti-interleukin-6 receptor monoclonal antibody, in Korean patients with active rheumatoid arthritis (RA) refractory to conventional disease modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX). Methods: The main study was a 24-week, randomized, double-blind, controlled trial that was followed by a 48-week, open-labeled, extension phase. TCZ (8 mg/kg) or placebo was intravenously administered every 4 weeks...
January 17, 2018: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29334270/secukinumab-in-multi-failure-psoriatic-patients-the-last-hope
#2
M Magnano, C Loi, A Patrizi, P Sgubbi, R Balestri, G Rech, L Tasin, C R Girardelli, A Conti, G Odorici, A Campanati, A M Offidani, F Bardazzi
Psoriasis is a multi-systemic chronic inflammatory disease that affects about 1.5-3% of the general population, of which almost 20% suffer from a moderate-severe form. Those patients can be treated with a systemic agent, and, in case of scarce response or contraindications, they may require a biologic therapy, such as tumor necrosis factor or interleukin-12/23 inhibitors. When also those agents fail, clinicians face a true therapeutic challenge. We report a case series of multi-failure 16 patients, successfully treated with secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A, recently approved for the treatment of plaque psoriasis, psoriatic arthritis and ankylosing spondylitis...
January 15, 2018: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29333938/structure-based-engineering-to-restore-high-affinity-binding-of-an-isoform-selective-anti-tgf%C3%AE-1-antibody
#3
Dana M Lord, Julie J Bird, Denise M Honey, Annie Best, Anna Park, Ronnie R Wei, Huawei Qiu
Metelimumab (CAT192) is a human IgG4 monoclonal antibody developed as a TGFβ1-specific antagonist. It was tested in clinical trials for the treatment of scleroderma but later terminated due to lack of efficacy. Subsequent characterization of CAT192 indicated that its TGFβ1 binding affinity was reduced by ∼50-fold upon conversion from the parental single-chain variable fragment (scFv) to IgG4. We hypothesized this result was due to decreased conformational flexibility of the IgG that could be altered via engineering...
January 15, 2018: MAbs
https://www.readbyqxmd.com/read/29333869/quantitation-of-saxitoxin-in-human-urine-using-immunocapture-extraction-and-lc-ms
#4
William A Bragg, Alaine Garrett, Elizabeth I Hamelin, Rebecca M Coleman, Katrina Campbell, Christopher T Elliott, Rudolph C Johnson
AIM: An immunomagnetic capture protocol for use with LC-MS was developed for the quantitation of saxitoxin (STX) in human urine. MATERIALS & METHODS: This method uses monoclonal antibodies coupled to magnetic beads. STX was certified reference material grade from National Research Council, Canada. Analysis was carried out using LC-MS. RESULTS: With an extraction efficiency of 80%, accuracy and precision of 93.0-100.2% and 5.3-12.6%, respectively, and a dynamic range of 1...
January 15, 2018: Bioanalysis
https://www.readbyqxmd.com/read/29333591/differential-inhibition-of-nav1-7-and-neuropathic-pain-by-hybridoma-produced-and-recombinant-monoclonal-antibodies-that-target-nav1-7-differential-activities-of-nav1-7-targeting-monoclonal-antibodies
#5
Sangsu Bang, Jiho Yoo, Xingrui Gong, Di Liu, Qingjian Han, Xin Luo, Wonseok Chang, Gang Chen, Sang-Taek Im, Yong Ho Kim, Judith A Strong, Ma-Zhong Zhang, Jun-Ming Zhang, Seok-Yong Lee, Ru-Rong Ji
The voltage-gated Na+ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na+ currents and pain and itch responses in mice. Here, we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1...
January 15, 2018: Neuroscience Bulletin
https://www.readbyqxmd.com/read/29332046/a-novel-antibody-targeting-tau-phosphorylated-at-serine-235-detects-neurofibrillary-tangles
#6
David Brici, Jürgen Götz, Rebecca M Nisbet
Alzheimer's disease is characterized by two main pathological hallmarks in the human brain: the extracellular deposition of amyloid-β as plaques and the intracellular accumulation of the hyperphosphorylated protein tau as neurofibrillary tangles (NFTs). Phosphorylated tau (p-tau) specific-antibodies and silver staining have been used to reveal three morphological stages of NFT formation: pre-NFTs, intraneuronal NFTs (iNFTs), and extraneuronal NFTs (eNFTs). Here we characterize a novel monoclonal antibody, RN235, which is specific for tau phosphorylated at serine 235, and detects iNFTs and eNFTs in brain tissue, suggesting that phosphorylation at this site is indicative of late stage changes in tau...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29330552/dosimetry-prediction-for-clinical-translation-of-64cu-pembrolizumab-immunopet-targeting-human-pd-1-expression
#7
Arutselvan Natarajan, Chirag B Patel, Frezghi Habte, Sanjiv S Gambhir
The immune checkpoint programmed death 1 receptor (PD-1) expressed on some tumor-infiltrating lymphocytes, and its ligand (PD-L1) expressed on tumor cells, enable cancers to evade the immune system. Blocking PD-1 with the monoclonal antibody pembrolizumab is a promising immunotherapy strategy. Thus, noninvasively quantifying the presence of PD-1 expression in the tumor microenvironment prior to initiation of immune checkpoint blockade may identify the patients likely to respond to therapy. We have developed a 64Cu-pembrolizumab radiotracer and evaluated human dosimetry...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330305/restricted-processing-of-cd16a-fc-%C3%AE-receptor-iiia-n-glycans-from%C3%A2-primary-human-nk-cells-impacts-structure-and-function
#8
Kashyap R Patel, Jacob T Roberts, Ganesh P Subedi, Adam W Barb
CD16a/Fc γ receptor IIIa is the most abundant antibody Fc receptor expressed on human natural killer(NK) cells and activates a protective cytotoxic response following engagement with antibody clustered on the surface of a pathogen or diseased tissue. Therapeutic monoclonal antibodies(mAbs) with greater Fc-mediated affinity for CD16a show superior therapeutic outcome, however, one significant factor that promotes antibody-CD16a interactions, the asparagine-linked carbohydrates(N-glycans), remains undefined...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29329880/novel-expression-of-cd11b-in-epithelial-ovarian-cancer-potential-therapeutic-target
#9
Ghassan M Saed, Nicole M Fletcher, Michael P Diamond, Robert T Morris, Nardhy Gomez-Lopez, Ira Memaj
OBJECTIVE: The objective of this study was to determine the expression, and effect of targeting CD11b with a monoclonal antibody in ovarian cancer cells. METHODS: CD11b expression was determined in epithelial ovarian cancer (EOC) cell lines and tissues by immunofluorescence and flow cytometry. Cytotoxicity of the CD11b antibody and synergism with chemothearapeutic drugs were determined by the MTT Cell Proliferation Assay in human macrophages, normal ovarian epithelial cells, and in both sensitive and chemoresistant EOC cell lines...
January 9, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29329556/cancer-immunotherapy-beyond-immune-checkpoint-inhibitors
#10
REVIEW
Julian A Marin-Acevedo, Aixa E Soyano, Bhagirathbhai Dholaria, Keith L Knutson, Yanyan Lou
Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized...
January 12, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29329202/epcam-immunotherapy-versus-specific-targeted-delivery-of-drugs
#11
REVIEW
Joanna Macdonald, Justin Henri, Kislay Roy, Emma Hays, Michelle Bauer, Rakesh Naduvile Veedu, Normand Pouliot, Sarah Shigdar
The epithelial cell adhesion molecule (EpCAM), or CD326, was one of the first cancer associated biomarkers to be discovered. In the last forty years, this biomarker has been investigated for use in personalized cancer therapy, with the first monoclonal antibody, edrecolomab, being trialled in humans more than thirty years ago. Since then, several other monoclonal antibodies have been raised to EpCAM and tested in clinical trials. However, while monoclonal antibody therapy has been investigated against EpCAM for almost 40 years as primary or adjuvant therapy, it has not shown as much promise as initially heralded...
January 12, 2018: Cancers
https://www.readbyqxmd.com/read/29328782/the-role-of-nivolumab-in-melanoma
#12
Fabio Gomes, Patricio Serra-Bellver, Paul Lorigan
The incidence of melanoma continues to rise worldwide. Prior to 2010, there had been no progress in the treatment of advanced melanoma in living memory. Since then, immunotherapy has become a standard of care in the treatment of advanced melanoma. Nivolumab is a fully human monoclonal antibody against PD-1, which is a negative regulatory checkpoint in the T cells. The clinical benefit of nivolumab as a single agent is well established, with response rates of ≥40%, durable responses and a favorable tolerability profile...
January 12, 2018: Future Oncology
https://www.readbyqxmd.com/read/29328423/cetuximab-enhances-cisplatin-induced-endoplasmic-reticulum-stress-associated-apoptosis-in-laryngeal-squamous-cell-carcinoma-cells-by-inhibiting-expression-of-txndc5
#13
Fusen Peng, Hailin Zhang, Youhong Du, Pingqing Tan
Cisplatin and cetuximab, an anti‑epidermal growth factor receptor (EGFR) monoclonal humanized antibody, have been used for treatment of laryngeal squamous cell carcinoma (LSCC). It has been demonstrated that cisplatin and inhibition of EGFR signaling may induce endoplasmic reticulum (ER) stress‑associated apoptosis. However, ER protein thioredoxin domain‑containing protein 5 (TXNDC5) reportedly protects cells from ER stress‑associated apoptosis. The present study investigated the interaction between cisplatin, cetuximab and TXNDC5 on ER stress‑associated apoptosis in LSCC cells...
January 5, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29328392/targeting-bladder-cancer-using-activated-t%C3%A2-cells-armed-with-bispecific-antibodies
#14
Juan Ma, Jing Ge, Xin Xue, Weigang Xiu, Pan Ma, Ximing Sun, Man Zhang
In the present study, we aimed to investigate whether EGFR or HER2 may serve as a target for T cell-mediated immunotherapy against human bladder cancer. Expression of EGFR and HER2 was detected on the surface of bladder cancer cells, including Pumc-91 and T24 cells, and their chemotherapeutic drug-resistant counterparts. Activated T cells (ATCs) were generated from healthy PBMCs that were stimulated by the combination of anti-CD3 monoclonal antibody and anti‑CD28 monoclonal antibody in the presence of interleukin-2 for 14 days...
January 11, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29327590/a-simple-strategy-for-rapid-and-sensitive-detection-of-avian-influenza-a-h7n9-virus-based-on-intensity-modulated-spr-biosensor-and-new-generated-antibody
#15
Ying-Feng Chang, Wen-Hung Wang, Yi-Wei Hong, Ruei-Yu Yuan, Kuan-Hsuan Chen, Yu-Wen Huang, Po-Liang Lu, Yen-Hsu Chen, Yi-Ming Arthur Chen, Li-Chen Su, Sheng-Fan Wang
A new reassortant avian influenza A H7N9 virus have emerged in China since 2013, causing human infection with high mortality. An accurate and timely diagnosis is crucial for controlling the outbreaks of the disease. We therefore propose a simple strategy for rapidly and sensitively detecting the H7N9 virus using an intensity-modulated surface plasmon resonance (IM-SPR) biosensor integrated with a new generated monoclonal antibody. The novel antibody exhibits significant specificity to recognize H7N9 virus compared with other clinical human influenza isolates (p<0...
January 12, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29327488/isolation-of-human-photoreceptor-precursors-via-a-cell-surface-marker-panel-from-stem-cell-derived-retinal-organoids-and-fetal-retinae
#16
Jörn Lakowski, Emily Welby, Dimitri Budinger, Fabiana Di Marco, Valentina Di Foggia, James W B Bainbridge, Kyle Wallace, David M Gamm, Robin R Ali, Jane C Sowden
Loss of photoreceptor cells due to retinal degeneration is one of the main causes of blindness in the developed world. Although there is currently no effective treatment, cell replacement therapy using stem-cell-derived photoreceptor cells may be a feasible future treatment option. In order to ensure safety and efficacy of this approach, robust cell isolation and purification protocols must be developed. To this end, we previously developed a biomarker panel for the isolation of mouse photoreceptor precursors from the developing mouse retina and mouse embryonic stem cell cultures...
January 12, 2018: Stem Cells
https://www.readbyqxmd.com/read/29324225/the-marburgvirus-neutralizing-human-monoclonal-antibody-mr191-targets-a-conserved-site-to-block-virus-receptor-binding
#17
Liam B King, Marnie L Fusco, Andrew I Flyak, Philipp A Ilinykh, Kai Huang, Bronwyn Gunn, Robert N Kirchdoerfer, Kathryn M Hastie, Amandeep K Sangha, Jens Meiler, Galit Alter, Alexander Bukreyev, James E Crowe, Erica Ollmann Saphire
Since their first identification 50 years ago, marburgviruses have emerged several times, with 83%-90% lethality in the largest outbreaks. Although no vaccines or therapeutics are available for human use, the human antibody MR191 provides complete protection in non-human primates when delivered several days after inoculation of a lethal marburgvirus dose. The detailed neutralization mechanism of MR191 remains outstanding. Here we present a 3.2 Å crystal structure of MR191 complexed with a trimeric marburgvirus surface glycoprotein (GP)...
January 10, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29322650/molecular-characterization-of-the-%C3%AE-amyloid-4-10-epitope-of-plaque-specific-a%C3%AE-antibodies-by-affinity-mass-spectrometry-using-alanine-site-mutation
#18
Raluca Ștefănescu, Loredana Lupu, Marilena Manea, Roxana E Iacob, Michael Przybylski
Alzheimer disease is a neurodegenerative disease affecting an increasing number of patients worldwide. Current therapeutic strategies are directed to molecules capable to block the aggregation of the β-amyloid(1-42) (Aβ) peptide and its shorter naturally occurring peptide fragments into toxic oligomers and amyloid fibrils. Aβ-specific antibodies have been recently developed as powerful antiaggregation tools. The identification and functional characterization of the epitope structures of Aβ antibodies contributes to the elucidation of their mechanism of action in the human organism...
January 2018: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29322476/negative-regulators-of-cell-death-pathways-in-cancer-perspective-on-biomarkers-and-targeted-therapies
#19
REVIEW
Ali Razaghi, Kirsten Heimann, Patrick M Schaeffer, Spencer B Gibson
Cancer is a primary cause of human fatality and conventional cancer therapies, e.g., chemotherapy, are often associated with adverse side-effects, tumor drug-resistance, and recurrence. Molecularly targeted therapy, composed of small-molecule inhibitors and immunotherapy (e.g., monoclonal antibody and cancer vaccines), is a less harmful alternative being more effective against cancer cells whilst preserving healthy tissues. Drug-resistance, however, caused by negative regulation of cell death signaling pathways, is still a challenge...
January 10, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29321326/the-amino-terminus-of-hsv-1-glycoprotein-k-gk-is-required-for-gb-binding-to-akt-release-of-intracellular-calcium-and-fusion-of-the-viral-envelope-with-plasma-membranes
#20
Farhana Musarrat, Nithya Jambunathan, Paul J F Rider, V N Chouljenko, K G Kousoulas
Previously, we have shown that the amino terminus of glycoprotein K (gK) binds to the amino terminus of gB and that deletion of the amino terminal 38 amino acids of gK prevents virus infection of mouse trigeminal ganglia after ocular infection and virus entry into neuronal axons. Recently, it has been shown that gB binds to Akt during virus entry and induces Akt phosphorylation and intracellular calcium release. Proximity ligation and two-way immunoprecipitation assays using monoclonal antibodies against gB and Akt-1 (phospho S473) confirmed that HSV-1(McKrae) gB interacted with Akt-1 (phospo S473) during virus entry into human neuroblastoma (SK-N-SH) cells and induced release of intracellular calcium...
January 10, 2018: Journal of Virology
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