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https://www.readbyqxmd.com/read/28527063/the-role-of-anti-cgrp-antibodies-in-the-pathophysiology-of-primary-headaches
#1
Piero Barbanti, Cinzia Aurilia, Luisa Fofi, Gabriella Egeo, Patrizia Ferroni
Calcitonin gene-related peptide (CGRP), a potent vasodilator and pain-signaling neuropeptide, is a validated therapeutic target for migraine and cluster headache. Four anti-CGRP monoclonal antibodies (mAbs) have been developed, representing the first specific, mechanism-based, migraine prophylactic treatment. CGRP mAbs demonstrated good efficacy coupled to excellent tolerability and safety in 5 phase II clinical trials. Notably, CGRP mAbs induced complete migraine remission in a patients' subset. To date, more than 20 phase III trials using CGRP mAbs for of episodic and chronic migraine and cluster headache prevention are ongoing...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28526034/differential-darc-ackr1-expression-distinguishes-venular-from-non-venular-endothelial-cells-in-murine-tissues
#2
Aude Thiriot, Carolina Perdomo, Guiying Cheng, Igor Novitzky-Basso, Sara McArdle, Jamie K Kishimoto, Olga Barreiro, Irina Mazo, Robinson Triboulet, Klaus Ley, Antal Rot, Ulrich H von Andrian
BACKGROUND: Intravascular leukocyte recruitment in most vertebrate tissues is restricted to postcapillary and collecting venules, whereas capillaries and arterioles usually support little or no leukocyte adhesion. This segmental restriction is thought to be mediated by endothelial, rather than hemodynamic, differences. The underlying mechanisms are largely unknown, in part because effective tools to distinguish, isolate, and analyze venular endothelial cells (V-ECs) and non-venular endothelial cells (NV-ECs) have been unavailable...
May 19, 2017: BMC Biology
https://www.readbyqxmd.com/read/28525961/passive-and-active-immunization-against-respiratory-syncytial-virus-for-the-young-and-old
#3
Tonya Villafana, Judith Falloon, M Pamela Griffin, Qing Zhu, Mark T Esser
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants worldwide and also causes significant disease in the elderly. Despite 60 years of RSV research and vaccine development, there is only one approved medicine to prevent RSV infections. Palivizumab, a monoclonal antibody (mAb) against the RSV fusion (F) protein, is indicated for preterm infants and children at high-risk for RSV infections. It is an active time in RSV vaccine and mAb development with 14 vaccines and 2 mAbs currently being tested in clinical trials as of 13 February 2017...
May 19, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28525755/antibodies-from-a-human-survivor-define-sites-of-vulnerability-for-broad-protection-against-ebolaviruses
#4
Anna Z Wec, Andrew S Herbert, Charles D Murin, Elisabeth K Nyakatura, Dafna M Abelson, J Maximilian Fels, Shihua He, Rebekah M James, Marc-Antoine de La Vega, Wenjun Zhu, Russell R Bakken, Eileen Goodwin, Hannah L Turner, Rohit K Jangra, Larry Zeitlin, Xiangguo Qiu, Jonathan R Lai, Laura M Walker, Andrew B Ward, John M Dye, Kartik Chandran, Zachary A Bornholdt
Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28523098/incb24360-epacadostat-a-highly-potent-and-selective-indoleamine-2-3-dioxygenase-1-ido1-inhibitor-for-immuno-oncology
#5
Eddy W Yue, Richard Sparks, Padmaja Polam, Dilip Modi, Brent Douty, Brian Wayland, Brian Glass, Amy Takvorian, Joseph Glenn, Wenyu Zhu, Michael Bower, Xiangdong Liu, Lynn Leffet, Qian Wang, Kevin J Bowman, Michael J Hansbury, Min Wei, Yanlong Li, Richard Wynn, Timothy C Burn, Holly K Koblish, Jordan S Fridman, Tom Emm, Peggy A Scherle, Brian Metcalf, Andrew P Combs
A data-centric medicinal chemistry approach led to the invention of a potent and selective IDO1 inhibitor 4f, INCB24360 (epacadostat). The molecular structure of INCB24360 contains several previously unknown or underutilized functional groups in drug substances, including a hydroxyamidine, furazan, bromide, and sulfamide. These moieties taken together in a single structure afford a compound that falls outside of "drug-like" space. Nevertheless, the in vitro ADME data is consistent with the good cell permeability and oral bioavailability observed in all species (rat, dog, monkey) tested...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28521640/antibody-mediated-immunotherapy-against-chronic-hepatitis-b-virus-infection
#6
Ying Gao, Tian-Ying Zhang, Quan Yuan, Ning-Shao Xia
The currently available drugs to treat hepatitis B virus (HBV) infection include interferons and nucleos(t)ide analogues, which can only induce disease remission and are inefficient for the functional cure of patients with chronic HBV infection (CHB). Since high titers of circulating hepatitis B surface antigen (HBsAg) may be essential to exhaust the host anti-HBV immune response and they cannot be significantly reduced by current drugs, new antiviral strategies aiming to suppress serum hepatitis B surface antigen (HBsAg) could help restore virus-specific immune responses and promote the eradication of the virus...
May 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28521303/emt-circulating-tumor-cells-detected-by-cell-surface-vimentin-are-associated-with-prostate-cancer-progression
#7
Arun Satelli, Izhar Batth, Zachary Brownlee, Abhishek Mitra, Shouhao Zhou, Hyangsoon Noh, Christina R Rojas, Heming Li, Qing H Meng, Shulin Li
Recent advances in the field of circulating tumor cells (CTC) have shown promise in this liquid biopsy-based prognosis of patient outcome. However, not all of the circulating cells are tumor cells, as evidenced by a lack of tumor-specific markers. The current FDA standard for capturing CTCs (CellSearch) relies on an epithelial marker and cells captured via CellSearch cannot be considered to have undergone EMT. Therefore, it is difficult to ascertain the presence and relevance of any mesenchymal or EMT-like CTCs...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28518105/murine-lymphocyte-labeling-by-64cu-antibody-receptor-targeting-for-in-vivo-cell-trafficking-by-pet-ct
#8
Sabrina H L Hoffmann, Andreas Maurer, Dorothea I Reck, Gerald Reischl, Bernd J Pichler, Manfred Kneilling, Christoph M Griessinger
This protocol illustrates the production of (64)Cu and the chelator conjugation/radiolabeling of a monoclonal antibody (mAb) followed by murine lymphocyte cell culture and (64)Cu-antibody receptor targeting of the cells. In vitro evaluation of the radiolabel and non-invasive in vivo cell tracking in an animal model of an airway delayed-type hypersensitivity reaction (DTHR) by PET/CT are described. In detail, the conjugation of a mAb with the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is shown...
April 29, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28518088/in-vitro-methods-for-comparing-target-binding-and-cdc-induction-between-therapeutic-antibodies-applications-in-biosimilarity-analysis
#9
Nohemi Salinas-Jazmín, Edith González-González, Luz X Vásquez-Bochm, Sonia M Pérez-Tapia, Marco A Velasco-Velázquez
Therapeutic monoclonal antibodies (mAbs) are relevant to the treatment of different pathologies, including cancers. The development of biosimilar mAbs by pharmaceutical companies is a market opportunity, but it is also a strategy to increase drug accessibility and reduce therapy-associated costs. The protocols detailed here describe the evaluation of target binding and CDC induction by rituximab in Daudi cells. These two functions require different structural regions of the antibody and are relevant to the clinical effect induced by rituximab...
May 4, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28515943/evaluation-of-dosing-strategy-for-pembrolizumab-for-oncology-indications
#10
Tomoko Freshwater, Anna Kondic, Malidi Ahamadi, Claire H Li, Rik de Greef, Dinesh de Alwis, Julie A Stone
BACKGROUND: Traditionally, most monoclonal antibodies (mAbs) have been dosed based on body weight because of perceived contribution of body size in pharmacokinetic variability. The same approach was used in the initial pembrolizumab studies; however, following availability of PK data, the need for weight-based dosing for pembrolizumab was reassessed. METHODS: A previously established population PK (popPK) model as well as exposure-response results from patients with advanced melanoma or non-small cell lung cancer (NSCLC) were used to evaluate the potential application of a fixed dosing regimen with the aim of maintaining pembrolizumab exposures within the range demonstrated to provide near maximal efficacy and acceptable safety...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28514851/blood-brain-barrier-penetrating-biologic-tnf-%C3%AE-inhibitor-for-alzheimer-s-disease
#11
Rudy Chang, Jillian Knox, Jae Chang, Aram Derbedrossian, Vitaly Vasilevko, David Cribbs, Ruben J Boado, William M Pardridge, Rachita Sumbria
OBJECTIVE: Tumor necrosis factor alpha (TNF-α) driven processes are involved at multiple stages of Alzheimer's disease (AD) pathophysiology and disease progression. Biologic TNF-α inhibitors (TNFIs) are the most potent class of TNFIs but cannot be developed for AD since these macromolecules do not cross the blood-brain barrier (BBB). A BBB-penetrating TNFI was engineered by the fusion of the extracellular domain of the type II human TNF receptor (TNFR) to a chimeric monoclonal antibody (MAb) against the mouse transferrin receptor (TfR), designated as the cTfRMAb-TNFR fusion protein...
May 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28514687/particulate-array-of-well-ordered-hiv-clade-c-env-trimers-elicits-neutralizing-antibodies-that-display-a-unique-v2-cap-approach
#12
Paola Martinez-Murillo, Karen Tran, Javier Guenaga, Gustaf Lindgren, Monika Àdori, Yu Feng, Ganesh E Phad, Néstor Vázquez Bernat, Shridhar Bale, Jidnyasa Ingale, Viktoriya Dubrovskaya, Sijy O'Dell, Lotta Pramanik, Mats Spångberg, Martin Corcoran, Karin Loré, John R Mascola, Richard T Wyatt, Gunilla B Karlsson Hedestam
The development of soluble envelope glycoprotein (Env) mimetics displaying ordered trimeric symmetry has ushered in a new era in HIV-1 vaccination. The recently reported native, flexibly linked (NFL) design allows the generation of native-like trimers from clinical isolates at high yields and homogeneity. As the majority of infections world-wide are of the clade C subtype, we examined responses in non-human primates to well-ordered subtype C 16055 trimers administered in soluble or high-density liposomal formats...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28513912/improving-theranostics-in-pancreatic-cancer
#13
Jeremy King, Michael Bouvet, Gagandeep Singh, John Williams
BACKGROUND: Pancreatic cancer is the fourth most deadly cancer in the United States, and is expected to be the second most deadly by 2030. The major difficulty in treating pancreatic cancer is the late onset of symptoms. Generally, patients show metastatic disease by the time of diagnosis, with a survival rate of 5% beyond 5 years. In patients without metastatic disease, surgical resection increases 5 year survival rate to 25%. The remaining 75% succumb to undetected metastases. Clearly, improvements to both detection, surgical intervention, and therapeutic strategies will be needed to improve patient outcome in pancreatic cancer...
May 17, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28512676/different-fermentation-processes-produced-variants-of-an-anti-cd52-monoclonal-antibody-that-have-divergent-in-vitro-and-in-vivo-characteristics
#14
Chao Zhuang, Chen Zheng, Yantian Chen, Zheng Huang, Yanchao Wang, Qiang Fu, Chen Zeng, Tong Wu, Liming Yang, Nianmin Qi
The anti-CD52 antibody has already been approved for the treatment of patients with resistant chronic lymphocytic leukemia, relapsing-remitting multiple sclerosis, and has demonstrable efficacy against stem cell transplantation rejection. A CHO cell line expressing a humanized anti-CD52 monoclonal antibody (mAb-TH) was cultivated in both fed-batch and perfusion modes, and then purified. The critical quality attributes of these mAb variants were characterized and the pharmacokinetics (PK) properties were investigated...
May 16, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28512240/sting-activation-reverses-lymphoma-mediated-resistance-to-antibody-immunotherapy
#15
Lekh N Dahal, Lang Dou, Khiyam Hussain, Rena Liu, Alexander Earley, Kerry L Cox, Salome Murinello, Ian Tracy, Francesco Forconi, Andrew J Steele, Patrick Duriez, Diego Gomez-Nicola, Jessica L Teeling, Martin J Glennie, Mark S Cragg, Stephen A Beers
Tumors routinely attract and co-opt macrophages to promote their growth, angiogenesis and metastasis. Macrophages are also the key effector cell for monoclonal antibody (mAb) therapies. Here we report that the tumor microenvironment creates an immunosuppressive signature on tumor-associated macrophages (TAM) which favors expression of inhibitory rather than activating Fcγ receptors (FcγR), thereby limiting the efficacy of mAb immunotherapy. We assessed a panel of TLR and STING agonists (a) for their ability to reprogram macrophages to a state optimal for mAb immunotherapy...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28507812/a-barf1-specific-mab-as-a-new-immunotherapeutic-tool-for-the-management-of-ebv-related-tumors
#16
Riccardo Turrini, Anna Merlo, Debora Martorelli, Damiana Antonia Faè, Roberta Sommaggio, Isabella Monia Montagner, Vito Barbieri, Oriano Marin, Paola Zanovello, Riccardo Dolcetti, Antonio Rosato
The use of monoclonal antibodies (mAb) for the diagnosis and treatment of malignancies is acquiring an increasing clinical importance, thanks to their specificity, efficacy and relative easiness of use. However, in the context of Epstein-Barr virus (EBV)-related malignancies, only cancers of B-cell origin can benefit from therapeutic mAb targeting specific B-cell lineage antigens. To overcome this limitation, we generated a new mAb specific for BARF1, an EBV-encoded protein with transforming and immune-modulating properties...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507083/frequency-and-epitope-specificity-of-anti-factor-viii-c1-domain-antibodies-in-acquired-and-congenital-hemophilia-a
#17
Joerg Kahle, Aleksander Orlowski, Diana Stichel, John F Healey, Ernest T Parker, Marc Jaquemin, Manuela Krause, Andreas Tiede, Dirk Schwabe, Pete Lollar, Christoph Königs
Several studies showed that neutralizing anti-factor VIII (fVIII) antibodies (inhibitors) in patients with acquired hemophilia A (AHA) and congenital hemophilia A (HA) are primarily directed to the A2 and C2 domains. In this study the frequency and epitope specificity of anti-C1 antibodies were analyzed in acquired and congenital hemophilia inhibitor patients (n=178). The domain specificity of antibodies was studied by homologue-scanning mutagenesis (HSM) with single human domain human/porcine fVIII proteins and antibody binding to human A2, C1 and C2 domains presented as human serum albumin (HSA) fusion proteins...
May 15, 2017: Blood
https://www.readbyqxmd.com/read/28506821/development-of-a-bioassay-as-a-measure-of-drozitumab-mediated-apoptosis-induced-by-soluble-fc-gamma-receptors
#18
Jeongsup Shim, Ally Huang, Aaron S Miller
Drozitumab is an agonistic therapeutic monoclonal antibody (mAb) against the pro-apoptotic death receptor 5 (DR5). In vitro cell killing assays using drozitumab have traditionally required cross-linking with anti-Fc antibody to amplify the pro-apoptotic signal, although drozitumab shows activity in in vivo tumor models without artificial cross-linking. Recently it has been shown that FcγR expressing cells play an important role in the activity of drozitumab by mediating cross-linking in vivo (Wilson et al...
May 12, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28506316/characterization-of-novel-omp31-antigenic-epitopes-of-brucella-melitensis-by-monoclonal-antibodies
#19
Jinfeng Li, Feihuan Hu, Shouyi Chen, Peifang Luo, Zuoping He, Wenjing Wang, Jean-Pierre Allain, Chengyao Li
BACKGROUND: Brucellosis is a severe zoonotic disease worldwide. Detection and identification of Brucella species are essential to prevent or treat brucellosis in humans and animals. The outer membrane protein-31 (Omp31) is a major protein of Brucellae except for B. abortus, while the Omp31 antigenic epitopes have not been extensively characterized yet. RESULTS: A total of 22 monoclonal antibodies (mAbs) were produced against Omp31 of Brucella (B.) melitensis, of which 13 recognized five linear epitopes, 7 reacted with semi-conformational epitopes and 2 reacted with conformational epitopes, respectively...
May 15, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28505517/a-modified-adenovirus-vector-mediated-antibody-screening-method-identifies-epha2-as-a-cancer-target
#20
Toshihiro Tanaka, Hiromi Yamada, Masahide Kuroki, Shohta Kodama, Kazuo Tamura, Yasushi Takamatsu
BACKGROUND: We constructed a genetically modified adenovirus vector incorporating an IgG Fc-binding motif from staphylococcal protein A, Z33 (Adv-FZ33). Adv-FZ33 allows an antibody to redirect the vector to a target molecule on the cell surface. We attempted to search for target antigen candidates and antibodies that allowed highly selective gene transduction into malignant tumors. METHODS: Hybridoma libraries producing monoclonal antibodies (mAbs) were screened that increased transduction efficiency in cancer cell lines after cross-linking with Adv-FZ33...
May 12, 2017: Translational Oncology
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