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Monoclonal antibodies

Christina Yacoob, Miles Darnell Lange, Kristen Cohen, Kanan Lathia, Junli Feng, Jolene Glenn, Sara Carbonetti, Brian Oliver, Vladimir Vigdorovich, David Noah Sather, Leonidas Stamatatos
Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models. Their elicitation by immunization is thus highly desirable. The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies. Env-based immunogens tested so far in various animal species and humans have elicited binding and autologous neutralizing antibodies but not bNAbs (with a few notable exceptions). The underlying reasons for this are not well understood despite intensive efforts to characterize the binding specificities of the elicited antibodies; mostly by employing serologic methodologies and monoclonal antibody isolation and characterization...
June 22, 2018: PLoS Pathogens
Qian Chen, Chaoying Hu, Yanmei Liu, Rong Song, Wenjing Zhu, Hongxin Zhao, Antonio Nino, Fan Zhang, Yun Liu
BACKGROUND: Denosumab is a fully human monoclonal antibody against receptor activator of nuclear factor kappa-B ligand, a cytokine essential for the formation, function and survival of osteoclasts. This study assessed the pharmacokinetics, pharmacodynamics, safety and tolerability of single-dose denosumab (60 and 120 mg) in healthy Chinese volunteers. METHODS: This randomized (3:3:2), single-blind, placebo-controlled study enrolled healthy Chinese volunteers to receive single subcutaneous injection of denosumab 60 mg, 120 mg, or placebo...
2018: PloS One
Jun Lai, Yun Wang, Shan-Shan Wu, Ding Ding, Ze-Yu Sun, Ying Zhang, Jie Zhou, Zhan Zhou, Ying-Chun Xu, Li-Qiang Pan, Shu-Qing Chen
Most tumor-associated proteins are located inside tumor cells and thus are not accessible to current marketed therapeutic monoclonal antibodies or their cytotoxic conjugates. Human leukocyte antigen (HLA) class I can present peptides derived from intracellular tumor-associated proteins and somatically mutated proteins on the cell's surface, forming an HLA/peptide complex as tumor-specific antigens for T cell receptor (TCR) recognition. Therefore, HLA-mediated presentation of intracellular tumor antigen peptides provides a viable way to distinguish tumor cells from normal cells, which is important for broadening antigen selection, especially for antibody-drug conjugates (ADCs) regarding their highly cytotoxic payload...
June 15, 2018: Biomaterials
Shahryar Khoshtinat Nikkhoi, Fatemeh Rahbarizadeh, Davoud Ahmadvand, Seyed Moein Moghimi
The variable domain of the heavy chain antibodies (VHHs) is the smallest (15 kDa) intact single domain antigen-binding fragment. VHHs often exhibit sub-nanomolar affinity for their designated targets and therefore are receiving increasing attention in molecular targeting and nanomedicine engineering. We cloned and expressed four non-overlapping anti-HER2 VHHs in a prokaryotic expression system that yielded periplasmic expression of disulfide-bonded VHHs. Purified VHHs, before and after thiolation, were characterized by Western blot and their functionality against the ecto-domain of HER2 receptor was confirmed by ELISA and flow cytometry...
June 19, 2018: European Journal of Pharmaceutical Sciences
Vina P Nguyen, Heather Landau, Karen Quillen, Dina Brauneis, Anthony C Shelton, Lisa Mendelson, Hafsa Rahman, J Mark Sloan, Shayna Sarosiek, Vaishali Sanchorawala
High dose melphalan and autologous stem cell transplantation (HDM/SCT) has been used in patients with light chain (AL) amyloidosis for over two decades now with durable responses, prolonged survival, and decreasing treatment related mortality. Historically patients with poorer baseline functional status, advanced age, renal compromise and cardiac involvement have been treated with a risk-adapted modified conditioning dose of melphalan (mHDM) of 100-140 mg/m2 prior to SCT. Due in part to these baseline characteristics, patients receiving mHDM/SCT have had poorer outcomes compared to patients receiving full dose of melphalan at 200 mg/m2 ...
June 19, 2018: Biology of Blood and Marrow Transplantation
Terence L Kirley, Andrew B Norman
Monoclonal antibodies are very important in modern therapeutics and constitute a substantial percentage of newly approved drugs. Every therapeutic monoclonal antibody must be analyzed for structural and functional integrity, and all protein heterogeneities need to be identified and quantified. The conformational stabilities of the monoclonal antibodies are also important for antibody storage and handling stabilities. One of the first and simplest of the structural analysis techniques utilized is SDS-PAGE, which can be performed both with and without prior reduction to break disulfide bonds...
June 19, 2018: Biochemical and Biophysical Research Communications
Hae Ja Shin, Woon Ki Lim
In efforts to speed up the assessment of microorganisms, researchers have sought to use bacteriophages as a biosensing tool, due to their host-specificity, wide abundance, and safety. However, the lytic cycle of the phage has limited its efficacy as a biosensor. Here, we cloned a fragment of tail protein J from phage lambda and characterized its binding with the host, E. coli K-12, and other microorganism. The N-terminus of J was fused with a His-tag (6HN-J), overexpressed, purified, and characterized using anti-His monoclonal antibodies...
June 22, 2018: Preparative Biochemistry & Biotechnology
Angela Barone, John Benktander, Christy Whiddon, Chunsheng Jin, Cesare Galli, Susann Teneberg, Michael E Breimer
BACKGROUND: Pericardial tissue from various animal species is utilized for the production of the bioprosthetic heart valves (BHV) used clinically. Experimental data show that the eventual breakdown of BHV is partly due to immunological interactions with carbohydrate tissue antigens. To understand these processes, we have examined the glycolipid-based carbohydrate antigens in naïve porcine, bovine, and equine pericardia. EXPERIMENTAL: Total non-acid and acid glycosphingolipid fractions were isolated from porcine, bovine, and equine pericardia, and individual glycolipid compounds were characterized by thin-layer chromatography, mass spectrometry, and binding of monoclonal antibodies, lectins and bacteria in chromatogram binding assays...
June 22, 2018: Xenotransplantation
Pratima Chowdary
Mechanisms of action of monoclonal antibodies against tissue factor pathway inhibitor (TFPI).
June 2018: Drugs
Yvette N Lamb, Emma D Deeks
Sarilumab (Kevzara® ), a monoclonal antibody against the interleukin-6 (IL-6) receptor, is approved in various countries, including the USA, those of the EU, and Japan, as a subcutaneous treatment administered every 2 weeks for moderately to severely active rheumatoid arthritis (RA) in adults who have responded inadequately to, or are intolerant of, one or more DMARDs. In placebo-controlled trials, sarilumab improved the signs and symptoms of RA, as well as physical function and health-related quality-of-life (HR-QOL), when administered in combination with conventional synthetic DMARD (csDMARD) therapy in patients with an inadequate response to methotrexate or an inadequate response to, or intolerance of, at least one tumour necrosis factor (TNF) inhibitor; benefits were sustained over ≤ 3 years' therapy in an open-label extension...
June 2018: Drugs
Elias Jabbour, Ching-Hon Pui, Hagop Kantarjian
Importance: Remarkable progress has occurred in understanding the pathophysiology and in developing improved personalized therapies in adult acute lymphoblastic leukemia (ALL). Observations: We searched MEDLINE (1990-2018), the American Society of Clinical Oncology, and American Society of Hematology websites (2010-2018). We used the search terms "acute lymphoblastic or lymphocytic leukemia" or "ALL." We largely selected publications in the past 5 years but did not exclude commonly referenced and highly regarded older publications...
June 21, 2018: JAMA Oncology
D Noto, A Giammanco, C M Barbagallo, A B Cefalù, M R Averna
Anti-pcsk9 (proprotein convertase subtilisin kexin 9) monoclonal antibodies (Mab) are novel, potent lipid-lowering drugs. They demonstrated to improve the lipid profile in high cardiovascular risk patients. Anti-pcsk9 Mab inhibit the targeted LDL-receptor degradation induced by pcsk9 protein and are able to reduce LDL cholesterol (LDL-C) levels on top of conventional lipid-lowering therapy.Though these drugs proved to be very safe in the short term, little is known about the possible long term effects, due to the short period of their marketing...
June 20, 2018: Cardiovascular Research
Maria Lia Scribano
The biologic antitumor necrosis factor alpha (anti-TNFα) agents have revolutionised the treatment of inflammatory bowel disease (IBD). However, some patients experience primary nonresponse, loss of response, or intolerance. Therefore, introducing a newer class of therapy with a mechanism of action that acts on different inflammatory pathways involved in IBD pathogenesis is appealing. Vedolizumab is a fully humanised monoclonal antibody that selectively targets α4β7 integrin. Based on the results of the pivotal clinical GEMINI trials, vedolizumab was approved for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD) refractory or intolerant to either conventional therapy or TNFα inhibitors...
June 21, 2018: World Journal of Gastroenterology: WJG
Sumathi Sivapalasingam, Mohamed Kamal, Rabih Slim, Romana Hosain, Weiping Shao, Randall Stoltz, Joseph Yen, Laura G Pologe, Yuan Cao, Michael Partridge, Giane Sumner, Leah Lipsich
BACKGROUND: REGN3470-3471-3479 is a co-formulated cocktail of three human monoclonal antibodies targeting three non-overlapping epitopes on Ebola virus. We investigated safety, tolerability, pharmacokinetics, and anti-drug antibodies in healthy adults. METHODS: This randomised, double-blind, placebo-controlled, dose-escalation study was done at a phase 1 unit in the USA. Healthy adults, aged 18-60 years, with a body-mass index of 18·0-30·0 kg/m2 were randomly assigned (3:1) to receive a single intravenous dose of REGN3470-3471-3479 or placebo on day 1 (baseline) in one of the four sequential ascending intravenous dose cohorts (3 mg/kg, 15 mg/kg, 60 mg/kg, and 150 mg/kg)...
June 18, 2018: Lancet Infectious Diseases
Tomoyuki Moriyama, Dai Kakiuchi, Luigi Grasso, David L Hutto, Danielle Fernando, Charles Schweizer
Farletuzumab is a humanized monoclonal antibody targeting human folate receptor alpha, which is being developed as an anti-cancer drug. A non-human primate reproductive study was conducted to evaluate whether it could cause any embryonic or fetal abnormalities. Farletuzumab was administered intravenously to pregnant cynomolgus monkeys (n = 16/group) at doses of 0 or 67.5 mg/kg once weekly during gestation day (GD) 20 through 97. C-section was performed on GD100 ± 2, and fetuses were evaluated for morphologic (external, visceral and skeletal) effects...
June 18, 2018: Reproductive Toxicology
Breanna Sheahan, Christopher M Dekaney
No abstract text is available yet for this article.
2018: Cellular and Molecular Gastroenterology and Hepatology
Nicholas R Smith, John R Swain, Paige S Davies, Alexandra C Gallagher, Michael S Parappilly, Catherine Z Beach, Philip R Streeter, Ian A Williamson, Scott T Magness, Melissa H Wong
Background & Aims: Continual renewal of the intestinal epithelium is dependent on active- and slow-cycling stem cells that are confined to the crypt base. Tight regulation of these stem cell populations maintains homeostasis by balancing proliferation and differentiation to support critical intestinal functions. The hierarchical relation of discrete stem cell populations in homeostasis or during regenerative epithelial repair remains controversial. Although recent studies have supported a model for the active-cycling leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)+ intestinal stem cell (ISC) functioning upstream of the slow-cycling B lymphoma Mo-MLV insertion region 1 homolog (Bmi1)-expressing cell, other studies have reported the opposite relation...
2018: Cellular and Molecular Gastroenterology and Hepatology
Ricardo L Pereira, Isis C Nascimento, Ana P Santos, Isabella E Y Ogusuku, Claudiana Lameu, Günter Mayer, Henning Ulrich
Although the term 'cancer' was still over two thousand years away of being coined, the first known cases of the disease date back to about 3000BC, in ancient Egypt. Five thousand years later, still lacking a cure, it has become one of the leading causes of death, killing over half a dozen million people yearly. So far, monoclonal antibodies are the most successful immune-therapy tools when it comes to fighting cancer. The number of clinical trials that use them has been increasing steadily during the past few years, especially since the Food and Drug Administration greenlit the use of the first immune-checkpoint blockade antibodies...
June 1, 2018: Oncotarget
Aafke Creemers, Eva A Ebbing, Gerrit K J Hooijer, Lisanne Stap, Rajni A Jibodh-Mulder, Susanne S Gisbertz, Mark I van Berge Henegouwen, Maurits L van Montfoort, Maarten C C M Hulshof, Kausilia K Krishnadath, Martijn G H van Oijen, Maarten F Bijlsma, Sybren L Meijer, Hanneke W M van Laarhoven
Trastuzumab, a monoclonal antibody against HER2, has become standard of care for metastatic HER2-overexpressing esophagogastric adenocarcinoma and is currently investigated as (neo)adjuvant treatment option in HER2-positive esophagogastric adenocarcinoma. The HER2 status is commonly determined on archived material of the primary tumor. However, this status may change over the course of treatment or disease progression. The aim of this study was to assess the dynamics of HER2 status in esophageal adenocarcinoma (EAC) in patients with resectable and recurrent disease, and to determine the associations of these changes with clinical outcome...
June 1, 2018: Oncotarget
Jiasen Xie, Zishan Zhou, Shunchang Jiao, Xiaokun Li
A chimeric antigen receptor (CAR) is a type of fusion protein that comprises an antigen-recognition domain and signaling domains. In the present study, a programmed death-ligand 1 (PD-L1)-specific CAR, comprised of a single-chain variable fragment (scFv) derived from a monoclonal antibody, co-stimulatory domains of cluster of differentiation (CD) 28 and 4-1BB and a T-cell-activation domain derived from CD3ζ, was designed. The construction was cloned and packaged into the lentiviral vector pLVX. Flow cytometry confirmed that peripheral blood mononuclear cells were efficiently transduced and that the CAR was successfully expressed on T cells...
July 2018: Oncology Letters
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