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https://www.readbyqxmd.com/read/28821924/-89-zr-labeled-nivolumab-for-imaging-of-t-cell-infiltration-in-a-humanized-murine-model-of-lung-cancer
#1
Christopher G England, Dawei Jiang, Emily B Ehlerding, Brian T Rekoske, Paul A Ellison, Reinier Hernandez, Todd E Barnhart, Douglas G McNeel, Peng Huang, Weibo Cai
PURPOSE: Nivolumab is a human monoclonal antibody specific for programmed cell death-1 (PD-1), a negative regulator of T-cell activation and response. Acting as an immune checkpoint inhibitor, nivolumab binds to PD-1 expressed on the surface of many immune cells and prevents ligation by its natural ligands. Nivolumab is only effective in a subset of patients, and there is limited evidence supporting its use for diagnostic, monitoring, or stratification purposes. METHODS: (89)Zr-Df-nivolumab was synthesized to map the biodistribution of PD-1-expressing tumor infiltrating T-cells in vivo using a humanized murine model of lung cancer...
August 19, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28821604/development-of-a-multiplexed-assay-for-oral-cancer-candidate-biomarkers-using-peptide-immunoaffinity-enrichment-and-targeted-mass-spectrometry
#2
Yung-Chin Hsiao, Lang-Ming Chi, Kun-Yi Chien, Wei-Fan Chiang, Szu-Fan Chen, Yao-Ning Chuang, Shih-Yu Lin, Chia-Chun Wu, Ya-Ting Chang, Lichieh Julie Chu, Yi-Ting Chen, Shu-Li Chia, Chih-Yen Chien, Kai-Ping Chang, Yu-Sun Chang, Jau-Song Yu
Oral cancer is one of the most common cancers worldwide, and there are currently no biomarkers approved for aiding its management. Although many potential oral cancer biomarkers have been discovered, very few have been verified in body fluid specimens in parallel to evaluate their clinical utility. The lack of appropriate multiplexed assays for chosen targets represents one of the bottlenecks to achieving this goal. In the present study, we develop a peptide immunoaffinity enrichment-coupled multiple reaction monitoring-mass spectrometry (SISCAPA-MRM) assay for verifying multiple reported oral cancer biomarkers in saliva...
August 18, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28820904/parametric-studies-of-metabolic-cooperativity-in-escherichia-coli-colonies-strain-and-geometric-confinement-effects
#3
Joseph R Peterson, John A Cole, Zaida Luthey-Schulten
Characterizing the complex spatial and temporal interactions among cells in a biological system (i.e. bacterial colony, microbiome, tissue, etc.) remains a challenge. Metabolic cooperativity in these systems can arise due to the subtle interplay between microenvironmental conditions and the cells' regulatory machinery, often involving cascades of intra- and extracellular signalling molecules. In the simplest of cases, as demonstrated in a recent study of the model organism Escherichia coli, metabolic cross-feeding can arise in monoclonal colonies of bacteria driven merely by spatial heterogeneity in the availability of growth substrates; namely, acetate, glucose and oxygen...
2017: PloS One
https://www.readbyqxmd.com/read/28820579/site-specific-conjugation-to-native-and-engineered-lysines-in-human-immunoglobulins-by-microbial-transglutaminase
#4
Jared Spidel, Benjamin Vaessen, Earl Albone, Xin Cheng, Arielle Verdi, J Bradford Kline
The use of microbial transglutaminase (MTG) to produce site-specific antibody-drug conjugates (ADCs) has thus far focused on transamidation of engineered acyl donor glutamine residues in an antibody based on the hypothesis that the lower specificity of MTG for acyl acceptor lysines may result in transamidation of multiple native lysine residues, thereby yielding heterogeneous products. We investigated the utilization of native IgG lysines as acyl acceptor sites for glutamine-based acyl donor substrates. Of the approximately 80 lysines in multiple recombinant IgG monoclonal antibodies (mAbs), none were transamidated...
August 18, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28820224/label-free-fluorescent-immunoassay-for-cu-2-ion-detection-based-on-uv-degradation-of-immunocomplex-and-metal-ion-chelates
#5
Qi Shu, Mengli Liu, Hui Ouyang, Zhifeng Fu
A mouse anti Cu(2+)-EDTA monoclonal antibody was used to capture EDTA chelated Cu(2+) ions. Then UV radiation was utilized to degrade immunocomplex and Cu(2+)-EDTA chelates to release free Cu(2+) ions. Based on their quenching effect to the fluorescent emission of CdSe/ZnS quantum dots, the released Cu(2+) ions could be detected with ideal specificity and high sensitivity.
August 18, 2017: Nanoscale
https://www.readbyqxmd.com/read/28820071/antibody-fragments-as-potential-biopharmaceuticals-for-cancer-therapy-success-and-limitations
#6
Roman V Kholodenko, Daniel V Kalinovsky, Igor I Doronin, Eugene D Ponomarev, Irina V Kholodenko
Monoclonal antibodies (mAbs) are an important class of therapeutic agents approved for the therapy of many types of malignancies. However, in certain cases applications of conventional mAbs have several limitations in anticancer immunotherapy. These limitations include insufficient efficacy and adverse effects. The antigen-binding fragments of antibodies have a considerable potential to overcome the disadvantages of conventional mAbs, such as poor penetration into solid tumors and Fc-mediated bystander activation of the immune system...
August 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28819991/infliximab-biosimilar-ct-p13-therapy-is-effective-and-safe-in-maintaining-remission-in-crohn-s-disease-and-ulcerative-colitis-experiences-from-a-single-center
#7
Klaudia Farkas, Mariann Rutka, Tamás Ferenci, Ferenc Nagy, Anita Bálint, Renáta Bor, Ágnes Milassin, Anna Fábián, Kata Szántó, Zsuzsanna Végh, Zsuzsanna Kürti, Péter L Lakatos, Zoltán Szepes, Tamás Molnár
BACKGROUND: CT-P13, the first biosimilar monoclonal antibody to infliximab (IFX), has been confirmed to be efficacious in inducing remission in inflammatory bowel diseases (IBD). The aim of this study was to evaluate the long-term efficacy and safety of CT-P13 therapy in Crohn's disease (CD) and ulcerative colitis (UC), and to identify predictors of sustained clinical response during a 54-week CT-P13 treatment period. PATIENTS AND METHODS: Patients with CD and UC, who were administered CT-P13, were prospectively enrolled...
August 18, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28819882/novel-immunotherapies-for-multiple-myeloma
#8
REVIEW
Mattia D'Agostino, Mario Boccadoro, Eric L Smith
PURPOSE OF REVIEW: The treatment landscape of multiple myeloma is rapidly changing; however, despite improvement in patients' survival, it still remains a largely incurable disease. One hallmark of myeloma is substantial immune dysfunction leading to an increased infection rate and the inability of immune surveillance to detect neoplastic cells. Here, we critically analyze clinical approaches to harness the immune system to overcome this defect with a focus on antibody based and adoptive cellular therapies...
August 18, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28819740/inotuzumab-ozogamicin-first-global-approval
#9
Yvette N Lamb
Intravenous inotuzumab ozogamicin (Besponsa(®); Pfizer) is an anti-CD22 monoclonal antibody-calicheamicin conjugate that binds to CD22-expressing tumour cells. Upon binding, the complex is internalised and the cytotoxic calicheamicin derivative is released inside the cell, inducing double-strand DNA breakage and subsequent cell death. In June 2017, the EMA granted inotuzumab ozogamicin approval as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukaemia (ALL)...
August 17, 2017: Drugs
https://www.readbyqxmd.com/read/28819723/guselkumab-first-global-approval
#10
Anthony Markham
Guselkumab (Tremfya™) is a human monoclonal IgG1λ antibody being developed by Janssen Biotech, Inc. that has been approved in the USA as a treatment for moderate-to-severe plaque psoriasis. Guselkumab inhibits the binding of interleukin 23 (IL-23) to its cell surface receptor, disrupting the type 17 helper T cell/IL-17 pathway. This article summarizes the milestones in the development of guselkumab leading to this first approval for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy...
August 17, 2017: Drugs
https://www.readbyqxmd.com/read/28819716/neurological-complications-of-therapeutic-monoclonal-antibodies-trends-from-oncology-to-rheumatology
#11
REVIEW
Chandler Gill, Stasia Rouse, Ryan D Jacobson
PURPOSE OF REVIEW: This review is to describe the scope of neurological complications associated with monoclonal antibody-based therapies, applied across medical specialties, to demonstrate the common and rare neurological syndromes that may be encountered in clinical practice according to the therapeutic agent being receive, and to explain appropriate work-up, diagnosis, and management of drug complications, as supported by the literature. RECENT FINDINGS: The number of commercially available, evidence-based therapeutic monoclonal antibodies continues to expand...
August 17, 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28819703/novel-prostate-cancer-immunotherapy-with-a-dna-encoded-anti-prostate-specific-membrane-antigen-monoclonal-antibody
#12
Kar Muthumani, Liron Marnin, Sagar B Kudchodkar, Alfredo Perales-Puchalt, Hyeree Choi, Sangya Agarwal, Veronica L Scott, Emma L Reuschel, Faraz I Zaidi, Elizabeth K Duperret, Megan C Wise, Kimberly A Kraynyak, Kenneth E Ugen, Niranjan Y Sardesai, J Joseph Kim, David B Weiner
Prostate-specific membrane antigen (PSMA) is expressed at high levels on malignant prostate cells and is likely an important therapeutic target for the treatment of prostate carcinoma. Current immunotherapy approaches to target PSMA include peptide, cell, vector or DNA-based vaccines as well as passive administration of PSMA-specific monoclonal antibodies (mAb). Conventional mAb immunotherapy has numerous logistical and practical limitations, including high production costs and a requirement for frequent dosing due to short mAb serum half-life...
August 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28819692/molecular-characterization-of-atypical-antigenic-variants-of-canine-rabies-virus-reveals-its-reintroduction-by-wildlife-vectors-in-southeastern-mexico
#13
Fabiola Garcés-Ayala, Nidia Aréchiga-Ceballos, Joanna M Ortiz-Alcántara, Elizabeth González-Durán, Sandra I Pérez-Agüeros, Alfonso Méndez-Tenorio, Belem Torres-Longoria, Irma López-Martínez, Lucía Hernández-Rivas, José Alberto Díaz-Quiñonez, José Ernesto Ramírez-González
Rabies is an infectious viral disease that is practically always fatal following the onset of clinical signs. In Mexico, the last case of human rabies transmitted by dogs was reported in 2006 and canine rabies has declined significantly due to vaccination campaigns implemented in the country. Here we report on the molecular characterization of six rabies virus strains found in Yucatan and Chiapas, remarkably, four of them showed an atypical reaction pattern when antigenic characterization with a reduced panel of eight monoclonal antibodies was performed...
August 17, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28819632/detection-of-islet-cell-immune-reactivity-with-low-glycemic-index-foods-is-this-a-concern-for-type-1-diabetes
#14
Datis Kharrazian, Martha Herbert, Aristo Vojdani
Dietary management of autoimmune diabetes includes low glycemic foods classified from the glycemic index, but it does not consider the role that immunoreactive foods may play with the immunological etiology of the disease. We measured the reactivity of either monoclonal or polyclonal affinity-purified antibodies to insulin, insulin receptor alpha, insulin receptor beta, zinc transporter 8 (ZnT8), tyrosine phosphatase-based islet antigen 2 (IA2), and glutamic acid decarboxylase (GAD) 65 and 67 against 204 dietary proteins that are commonly consumed...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28819070/claudin-5-binders-enhance-permeation-of-solutes-across-the-blood-brain-barrier-in-a-mammalian-model
#15
Yosuke Hashimoto, Keisuke Shirakura, Yoshiaki Okada, Hiroyuki Takeda, Kohki Endo, Maki Tamura, Akihiro Watari, Yoshifusa Sadamura, Tatsuya Sawasaki, Takefumi Doi, Kiyohito Yagi, Masuo Kondoh
A current bottleneck in the development of central nervous system (CNS) drugs is the lack of drug delivery systems targeting the CNS. The intercellular space between endothelial cells of the blood brain barrier (BBB) is sealed by complex protein-based structures called tight junctions (TJs). Claudin-5, a tetra-transmembrane protein is a key component of the TJ seal that prevents the paracellular diffusion of drugs into the CNS. In the present study, to investigate whether CLDN-5 binders can be used for delivery of drugs to the CNS, we generated monoclonal antibodies specific to the extracellular domains of CLDN-5...
August 17, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28819049/a-comparison-of-protein-stability-in-prefillable-syringes-made-of-glass-and-plastic
#16
Lloyd Waxman, Vinod D Vilivalam
The development of protein therapeutics requires stabilization of these labile molecules during shipment and storage. Biologics, particularly monoclonal antibodies, are frequently packaged at high concentration in prefillable syringes traditionally made of glass. However, some biologics are unstable in glass due to sensitivity to silicone oil, tungsten, glue or metal ions. Syringes made from the plastic cyclic olefin polymer, Daikyo Crystal Zenith® (CZ), with a Flurotec-laminated piston have none of these issues...
August 17, 2017: PDA Journal of Pharmaceutical Science and Technology
https://www.readbyqxmd.com/read/28819024/trastuzumab-increases-her2-uptake-and-cross-presentation-by-dendritic-cells
#17
Victor A Gall, Anne V Philips, Na Qiao, Karen Clise-Dwyer, Alexander A Perakis, Mao Zhang, Guy Travis Clifton, Pariya Sukhumalchandra, Qing Ma, Sangeetha M Reddy, Dihua Yu, Jeffrey J Molldrem, George E Peoples, Gheath Alatrash, Elizabeth A Mittendorf
Early phase clinical trials evaluating CD8+ T cell-eliciting, HER2-derived peptide vaccines administered to HER2-positive breast cancer patients in the adjuvant setting suggest synergy between the vaccines and trastuzumab, the monoclonal antibody targeting the HER2 protein. Among 60 patients enrolled on clinical trials evaluating the E75+GM-CSF and GP2+GM-CSF vaccines, there have been no recurrences in patients vaccinated after receiving trastuzumab as part of standard therapy in the per treatment analyses conducted after a median follow-up of greater than 34 months...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28818634/mining-na%C3%A3-ve-rabbit-antibody-repertoires-by-phage-display-for-monoclonal-antibodies-of-therapeutic-utility
#18
Haiyong Peng, Thomas Nerreter, Jing Chang, Junpeng Qi, Xiuling Li, Pabalu Karunadharma, Gustavo Martinez, Mohammad Fallahi, Jo Soden, Jim Freeth, Roger R Beerli, Ulf Grawunder, Michael Hudecek, Christoph Rader
Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but in some cases also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity...
August 14, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28818019/pembrolizumab-in-the-treatment-of-metastatic-non-small-cell-lung-cancer-a-review-of-current-evidence
#19
Karim Rihawi, Francesco Gelsomino, Francesca Sperandi, Barbara Melotti, Michelangelo Fiorentino, Laura Casolari, Andrea Ardizzoni
Immune checkpoint inhibitors (ICPIs) are considered one of the most important breakthroughs in cancer treatment of the past decade; notably, different studies of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have reported impressive clinical activity and durable responses in patients with advanced non-small cell lung cancer (NSCLC). These findings have led to the changing of the current therapeutic algorithm of advanced NSCLC, adding a new standard first-line treatment option for patients with PD-L1-positive tumors...
August 1, 2017: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/28817679/increased-half-life-and-enhanced-potency-of-fc-modified-human-pcsk9-monoclonal-antibodies-in-primates
#20
Yijun Shen, Hua Li, Li Zhao, Gang Li, Ben Chen, Qingsong Guo, Bei Gao, Jinsong Wu, Tong Yang, Li Jin, Yong Su
Blocking proprotein convertase subtilisin kexin type 9 (PCSK9) binding to low-density lipoprotein receptor (LDLR) can profoundly lower plasma LDL levels. Two anti-PCKS9 monoclonal antibodies (mAbs), alirocumab and evolocumab, were approved by the FDA in 2015. The recommended dose is 75 mg to 150 mg every two weeks for alirocumab and 140mg every two weeks or 420 mg once a month for evolocumab. This study attempted to improve the pharmacokinetic properties of F0016A, an IgG1 anti-PCKS9 mAb, to generate biologically superior molecules...
2017: PloS One
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