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antibody design

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https://www.readbyqxmd.com/read/28822314/a-portable-smart-phone-device-for-rapid-and-sensitive-detection-of-e-coli-o157-h7-in-yoghurt-and-egg
#1
Mohamed Maarouf Ali Zeinhom, Yijia Wang, Yang Song, Mei-Jun Zhu, Yuehe Lin, Dan Du
The detection of E. coli O157:H7 in foods has held the attention of many researchers because of the seriousness attributed to this pathogen. In this study, we present a simple, sensitive, rapid and portable smartphone based fluorescence device for E. coli O157:H7 detection. This field-portable fluorescent imager on the smartphone involves a compact laser-diode-based photosource, a long-pass (LP) thin-film interference filter and a high-quality insert lenses. The design of the device provided a low noise to background imaging system...
August 4, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28822058/immune-dysfunction-in-non-hodgkin-lymphoma-avenues-for-new-immunotherapy-based-strategies
#2
REVIEW
Lorenzo Falchi
PURPOSE OF THIS REVIEW: The present review focuses on key aspects of non-Hodgkin lymphoma (NHL) evasion of immune surveillance and how these can be leveraged to devise effective immunotherapy strategies. RECENT FINDINGS: In recent years, significant progress has been made in the field of cancer immunotherapy. In particular, the remarkable clinical results of anti-programmed death (PD)-1/PD-ligand (L)1 antibodies are revolutionizing the treatment approach to multiple solid and hematologic tumors...
August 18, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28821924/-89-zr-labeled-nivolumab-for-imaging-of-t-cell-infiltration-in-a-humanized-murine-model-of-lung-cancer
#3
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/28821561/zika-virus-activates-de-novo-and-cross-reactive-memory-b-cell-responses-in-dengue-experienced-donors
#4
Thomas F Rogers, Eileen C Goodwin, Bryan Briney, Devin Sok, Nathan Beutler, Alexander Strubel, Rebecca Nedellec, Khoa Le, Michael E Brown, Dennis R Burton, Laura M Walker
Zika virus (ZIKV) shares a high degree of homology with dengue virus (DENV), suggesting that preexisting immunity to DENV could affect immune responses to ZIKV. We have tracked the evolution of ZIKV-induced B cell responses in three DENV-experienced donors. The acute antibody (plasmablast) responses were characterized by relatively high somatic hypermutation and a bias toward DENV binding and neutralization, implying the early activation of DENV clones. A DENV-naïve donor in contrast showed a classical primary plasmablast response...
August 18, 2017: Science Immunology
https://www.readbyqxmd.com/read/28820943/the-active-site-flexibility-of-mycobacterium-tuberculosis-isocitrate-lyase-in-dimer-form
#5
Yie-Vern Lee, Sybing Choi, Habibah Wahab, Yee Siew Choong
Tuberculosis (TB) still remains as global threat due to the emerging of drug resistant strain. Instead of focus on drug target of active stage TB, we are highlighting the isocitrate lyase (ICL) at the dormant stage TB. ICL is one of the persistent factors for Mycobacterium tuberculosis (MTB) to survive during dormant phase. In addition, the absent of ICL in human has made ICL a potential drug target for TB therapy. However, the dynamics details of ICL which could give insights to the ICL-ligand interaction is yet to be solved...
August 18, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28820730/knowledge-of-hepatitis-b-virus-infection-and-its-control-practices-among-dental-students-in-an-indian-city
#6
Vishal Khandelwal, Sushma Khandelwal, Neetu Gupta, Ullal Anand Nayak, Namrata Kulshreshtha, Sudhindra Baliga
Background Hepatitis B virus infection is a general cause of chronic hepatitis, liver cirrhosis and hepato-cellular carcinoma worldwide. It is highly contagious. It is an important reason for morbidity and mortality in the Indian population. Oral health professionals are at the highest risk. Vaccination for hepatitis B can prevent this deadly disease. Methods The present study was designed to evaluate the degree of awareness, knowledge of hepatitis B infection and status of hepatitis B vaccination among dental students...
August 18, 2017: International Journal of Adolescent Medicine and Health
https://www.readbyqxmd.com/read/28819487/an-evaluation-of-wb123-antibody-elisa-in-individuals-treated-with-ivermectin-and-albendazole-and-implementation-challenges-in-africa
#7
Dziedzom Komi de Souza, Irene Offei Owusu, Joseph Otchere, Michelle Adimazoya, Kwadwo Frempong, Collins Stephen Ahorlu, Daniel Adjei Boakye, Michael David Wilson
The development of antibody testing for the diagnosis of lymphatic filariasis (LF) is intended to enhance the monitoring and evaluation activities of the Global Program for the Elimination of LF. This is due to the fact that antibody tests are expected to be the most sensitive at detecting exposure to LF compared to antigen that takes longer to develop. To this end a new antibody-based enzyme linked immunosorbent assay (ELISA) to Wuchereria bancrofti antigen Wb123 has been developed and further designed into a point of care rapid diagnostic test, under evaluation...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28817175/drug-development-for-breast-colorectal-and-non-small-cell-lung-cancers-from-1979-to-2014
#8
Nancy A Nixon, Omar F Khan, Hasiba Imam, Patricia A Tang, Jose Monzon, Haocheng Li, Gavin Sun, Doreen Ezeife, Sunil Parimi, Scot Dowden, Vincent C Tam
BACKGROUND: Understanding the drug development pathway is critical for streamlining the development of effective cancer treatments. The objective of the current study was to delineate the drug development timeline and attrition rate of different drug classes for common cancer disease sites. METHODS: Drugs entering clinical trials for breast, colorectal, and non-small cell lung cancer were identified using a pharmaceutical business intelligence database. Data regarding drug characteristics, clinical trials, and approval dates were obtained from the database, clinical trial registries, PubMed, and regulatory Web sites...
August 17, 2017: Cancer
https://www.readbyqxmd.com/read/28814907/new-prognostic-biomarkers-and-therapeutic-effect-of-bevacizumab-for-patients-with-non-small-cell-lung-cancer
#9
Maiko Niki, Takashi Yokoi, Takayasu Kurata, Shosaku Nomura
BACKGROUND: Several biomarkers have emerged as potential prognostic and predictive markers for non-small-cell lung cancer (NSCLC). Successful inhibition of angiogenesis with the antivascular endothelial growth factor antibody, bevacizumab, has improved the efficacy seen with standard cytotoxic therapy of NSCLC. However, despite such enhanced treatment strategies, the prognosis for patients with advanced NSCLC remains poor. PATIENTS AND METHODS: We assessed potential biomarkers in 161 NSCLC patients and 42 control patients...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28814834/intracellular-trafficking-of-new-anticancer-therapeutics-antibody-drug-conjugates
#10
REVIEW
Muhammad Kalim, Jie Chen, Shenghao Wang, Caiyao Lin, Saif Ullah, Keying Liang, Qian Ding, Shuqing Chen, Jinbiao Zhan
Antibody-drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28813678/therapeutic-antibodies-to-ganglioside-gd2-evolved-from-highly-selective-germline-antibodies
#11
Eric Sterner, Megan L Peach, Marc C Nicklaus, Jeffrey C Gildersleeve
Antibodies play a crucial role in host defense and are indispensable research tools, diagnostics, and therapeutics. Antibody generation involves binding of genomically encoded germline antibodies followed by somatic hypermutation and in vivo selection to obtain antibodies with high affinity and selectivity. Understanding this process is critical for developing monoclonal antibodies, designing effective vaccines, and understanding autoantibody formation. Prior studies have found that antibodies to haptens, peptides, and proteins evolve from polyspecific germline antibodies...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813656/fc%C3%AE-receptor-function-and-the-design-of-vaccination-strategies
#12
REVIEW
Stylianos Bournazos, Jeffrey V Ravetch
Through specific interactions with distinct types of Fcγ receptors (FcγRs), the Fc domain of immunoglobulin G (IgG) mediates a wide spectrum of immunological functions that influence both innate and adaptive responses. Recent studies indicate that IgG Fc-FcγR interactions are dynamically regulated during an immune response through the control of the Fc-associated glycan structure and Ig subclass composition on the one hand and selective FcγR expression on immune cells on the other, which together determine the capacity of IgG to interact in a cell-type-specific manner with specific members of the FcγR family...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28812955/igg-cooperativity-is-there-allostery-implications-for-antibody-functions-and-therapeutic-antibody-development
#13
Danlin Yang, Rachel Kroe-Barrett, Sanjaya Singh, Christopher J Roberts, Thomas M Laue
A central dogma in immunology is that an antibody's in vivo functionality is mediated by two independent events: antigen binding by the variable (V) region, followed by effector activation by the constant (C) region. However, this view has recently been challenged by reports suggesting allostery exists between the two regions, triggered by conformational changes or configurational differences. The possibility of allosteric signals propagating through the IgG domains complicates our understanding of the antibody structure-function relationship, and challenges the current subclass selection process in therapeutic antibody design...
August 16, 2017: MAbs
https://www.readbyqxmd.com/read/28812882/aberrantly-large-single-channel-conductance-of-polyhistidine-arm-containing-protein-nanopores
#14
Avinash Kumar Thakur, Motahareh Ghahari Larimi, Kristin Gooden, Liviu Movileanu
There have been only a few studies reporting on the impact of polyhistidine affinity tags on the structure, function, and dynamics of proteins. Because of their relatively short size, they are often assumed to have little or no effect on the conformation and activity of a protein. Here, using membrane protein design and single-molecule electrophysiology, we determined that the presence of a hexahistidine arm at the N-terminus of a truncated FhuA-based protein nanopore, leaving the C-terminus untagged, produces an unusual increase in the unitary conductance up to ~8 nS in 1 M KCl...
August 16, 2017: Biochemistry
https://www.readbyqxmd.com/read/28811153/the-design-of-target-specific-antibodies-scfv-by-applying-de-novo-workflow-case-study-on-bmr1-antigen-from-brugia-malayi
#15
Bee Yin Khor, Theam Soon Lim, Rahmah Noordin, Yee Siew Choong
De novo approach was applied to design single chain fragment variable (scFv) for BmR1, a recombinant antigen from Bm17DIII gene which is the primary antigen used for the detection of anti-BmR1 IgG4 antibodies in the diagnostic of lymphatic filariasis. Three epitopes of the BmR1 was previously predicted form an ab initio derived three-dimensional structure. A collection of energetically favourable conformations was generated via hot-spot-centric approach. This resulted in a set of three different scFv scaffolds used to compute the high shape complementary conformations via dock-and-design approach with the predicted epitopes of BmR1...
July 19, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28811102/high-resolution-separations-of-charge-variants-and-disulfide-isomers-of-monoclonal-antibodies-and-antibody-drug-conjugates-using-ultra-high-voltage-capillary-electrophoresis-with-high-electric-field-strength
#16
W Hampton Henley, Yan He, J Scott Mellors, Nicholas G Batz, J Michael Ramsey, James W Jorgenson
Ultra-high voltage capillary electrophoresis with high electric field strength has been applied to the separation of the charge variants, drug conjugates, and disulfide isomers of monoclonal antibodies. Samples composed of many closely related species are difficult to resolve and quantify using traditional analytical instrumentation. High performance instrumentation can often save considerable time and effort otherwise spent on extensive method development. Ideally, the resolution obtained for a given CE buffer system scales with the square root of the applied voltage...
July 29, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28810837/phase-i-dose-escalation-study-of-pazopanib-combined-with-bevacizumab-in-patients-with-metastatic-renal-cell-carcinoma-or-other-advanced-tumors
#17
Sylvie Négrier, David Pérol, Rastislav Bahleda, Antoine Hollebecque, Etienne Chatelut, Helen Boyle, Philippe Cassier, Séverine Metzger, Ellen Blanc, Jean-Charles Soria, Bernard Escudier
BACKGROUND: Vascular endothelial growth factor (VEGF) directed therapies are being used in a large number of advanced tumors. Metastatic renal cell carcinoma (mRCC) is highly dependent on the VEGF pathway; VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKI) and humanized VEGF monoclonal antibody have been registered for clinical use in advanced renal cell carcinoma. The VEGFR TKI, pazopanib, with a rather manageable toxicity profile, was preferred to sunitinib by mRCC patients. We investigate the combination of pazopanib and bevacizumab to determine the maximum tolerated dose (MTD) in mRCC and other advanced solid tumors...
August 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28809825/analysis-of-histone-antibody-specificity-with-peptide-microarrays
#18
Evan M Cornett, Bradley M Dickson, Scott B Rothbart
Post-translational modifications (PTMs) on histone proteins are widely studied for their roles in regulating chromatin structure and gene expression. The mass production and distribution of antibodies specific to histone PTMs has greatly facilitated research on these marks. As histone PTM antibodies are key reagents for many chromatin biochemistry applications, rigorous analysis of antibody specificity is necessary for accurate data interpretation and continued progress in the field. This protocol describes an integrated pipeline for the design, fabrication and use of peptide microarrays for profiling the specificity of histone antibodies...
August 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28807998/immunogenicity-and-structures-of-a-rationally-designed-prefusion-mers-cov-spike-antigen
#19
Jesper Pallesen, Nianshuang Wang, Kizzmekia S Corbett, Daniel Wrapp, Robert N Kirchdoerfer, Hannah L Turner, Christopher A Cottrell, Michelle M Becker, Lingshu Wang, Wei Shi, Wing-Pui Kong, Erica L Andres, Arminja N Kettenbach, Mark R Denison, James D Chappell, Barney S Graham, Andrew B Ward, Jason S McLellan
Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28807568/function-of-novel-anti-cd19-chimeric-antigen-receptors-with-human-variable-regions-is-affected-by-hinge-and-transmembrane-domains
#20
Leah Alabanza, Melissa Pegues, Claudia Geldres, Victoria Shi, Jed J W Wiltzius, Stuart A Sievers, Shicheng Yang, James N Kochenderfer
Anti-CD19 chimeric antigen receptor (CAR) T cells have caused remissions of B cell malignancies, but problems including cytokine-mediated toxicity and short persistence of CAR T cells in vivo might limit the effectiveness of anti-CD19 CAR T cells. Anti-CD19 CARs that have been tested clinically had single-chain variable fragments (scFvs) derived from murine antibodies. We have designed and constructed novel anti-CD19 CARs containing a scFv with fully human variable regions. T cells expressing these CARs specifically recognized CD19(+) target cells and carried out functions including degranulation, cytokine release, and proliferation...
July 27, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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