journal
MENU ▼
Read by QxMD icon Read
search

MAbs

journal
https://www.readbyqxmd.com/read/28165915/humanization-of-rabbit-monoclonal-antibodies-via-grafting-combined-kabat-imgt-paratome%C3%A2-complementarity-determining-regions-rationale-and-examples
#1
Yi-Fan Zhang, Mitchell Ho
Rabbit monoclonal antibodies (RabMAbs) can recognize diverse epitopes, including those poorly immunogenic in mice and humans. However, there have been only a few reports on RabMAb humanization, an important antibody engineering step usually done before clinical applications are investigated. To pursue a general method for humanization of RabMAbs, we analyzed the complex structures of five RabMAbs with their antigens currently available in the Protein Data Bank, and identified antigen-contacting residues on the rabbit Fv within the 6 Angstrom distance to its antigen...
February 6, 2017: MAbs
https://www.readbyqxmd.com/read/28136017/the-impact-of-trisulfide-modification-of-antibodies-on-the-properties-of-antibody-drug-conjugates-manufactured-using-thiol-chemistry
#2
Renpeng Liu, Xuan Chen, Junia Dushime, Megan Bogalhas, Alexandru C Lazar, Thomas Ryll, Lintao Wang
Antibody-drug conjugates (ADCs) are promising biotherapeutic agents for the treatment of cancer. The careful monitoring of critical quality attributes is important for ADCs' development, manufacturing and production. In this work, the effect of the presence of a trisulfide bond in the monoclonal antibody (mAb) conjugated to DM4 cytotoxic payload through a disulfide-bond linker sulfo-SPDB (sSPDB) was investigated. Three lots of antibody containing variable levels of trisulfide bonds were used. The identity and levels of trisulfide bonds were determined by liquid chromatography/ mass spectrometry (MS)/MS analysis...
January 31, 2017: MAbs
https://www.readbyqxmd.com/read/28125318/in-silico-prediction-of-concentration-dependent-viscosity-curves-for-monoclonal-antibody-solutions
#3
Dheeraj S Tomar, Li Li, Matthew P Broulidakis, Nicholas G Luksha, Christopher T Burns, Satish K Singh, Sandeep Kumar
Early stage developability assessments of monoclonal antibody (mAb) candidates can help reduce risks and costs associated with their product development. Forecasting viscosity of highly concentrated mAb solutions is an important aspect of such developability assessments. Reliable predictions of concentration-dependent viscosity behaviors for mAb solutions in platform formulations can help screen or optimize drug candidates for flexible manufacturing and drug delivery options. Here, we present a computational method to predict concentration-dependent viscosity curves for mAbs solely from their sequence-structural attributes...
January 26, 2017: MAbs
https://www.readbyqxmd.com/read/28125314/bisfabs-tools-for-rapidly-screening-hybridoma-iggs-for-their-activities-as-bispecific-antibodies
#4
Sanket Patke, Ji Li, Peiyin Wang, Dion Slaga, Jennifer Johnston, Sunil Bhakta, Siler Panowski, Liping L Sun, Teemu Junttila, Justin M Scheer, Diego A Ellerman
Bispecific antibodies are a growing class of therapeutic molecules. Many of the current bispecific formats require DNA engineering to convert the parental monoclonal antibodies into the final bispecific molecules. We describe here a method to generate bispecific molecules from hybridoma IgGs in 3-4 days using chemical conjugation of antigen-binding fragments (Fabs) (bisFabs). Proteolytic digestion conditions for each IgG isotype were analyzed to optimize the yield and quality of the final conjugates. The resulting bisFabs showed no significant amounts of homodimers or aggregates...
January 26, 2017: MAbs
https://www.readbyqxmd.com/read/28106519/subunit-mass-analysis-for-monitoring-antibody-oxidation
#5
Izabela Sokolowska, Jingjie Mo, Jia Dong, Michael J Lewis, Ping Hu
Methionine oxidation is a common posttranslational modification (PTM) of monoclonal antibodies (mAbs). Oxidation can reduce the in-vivo half-life, efficacy and stability of the product. Peptide mapping is commonly used to monitor the levels of oxidation, but this is a relatively time-consuming method. A high-throughput, automated subunit mass analysis method was developed to monitor antibody methionine oxidation. In this method, samples were treated with IdeS, EndoS and dithiothreitol to generate three individual IgG subunits (light chain, Fd' and single chain Fc)...
January 20, 2017: MAbs
https://www.readbyqxmd.com/read/28102754/enhancement-of-antibody-functions-through-fc-multiplications
#6
Qun Wang, Yan Chen, Mark Pelletier, Romana Cvitkovic, Jessica Bonnell, Chien-Ying Chang, Adem C Koksal, Ellen O'Connor, Xizhe Gao, Xiang-Qing Yu, Herren Wu, C Kendall Stover, William F Dall'Acqua, Xiaodong Xiao
Antibodies carry out a plethora of functions through their crystallizable fragment (Fc) regions, which can be naturally tuned by the adoption of several isotypes and post-translational modifications. Protein engineering enables further Fc function modulations through modifications of the interactions between the Fc and its functional partners, including FcγR, FcRn, complement complex, and additions of auxiliary functional units. Due to the many functions embedded within the confinement of an Fc, a suitable balance must be maintained for a therapeutic antibody to be effective and safe...
January 19, 2017: MAbs
https://www.readbyqxmd.com/read/28095113/quantitative-analysis-of-cell-surface-antigen-antibody-interaction-using-gaussia-princeps-luciferase-antibody-fusion-proteins
#7
Juliane Kums, Johannes Nelke, Benedikt Rüth, Viktoria Schäfer, Daniela Siegmund, Harald Wajant
Cell surface antigen-specific antibodies are of substantial diagnostic and therapeutic importance. The binding properties of such antibodies are usually evaluated by cell-free assays, in particular surface plasmon resonance (SPR) analysis, or flow cytometry. SPR analyses allow the detailed quantitative and dynamic evaluation of the binding properties of antibodies, but need purified, typically recombinantly produced antigens. It can, however, be difficult to produce the required antigen. Furthermore, cellular factors influencing the antigen-antibody interaction are not considered by this method...
January 17, 2017: MAbs
https://www.readbyqxmd.com/read/28055305/generation-of-a-highly-diverse-panel-of-antagonistic-chicken-monoclonal-antibodies-against-the-gip-receptor
#8
Jennifer D Könitzer, Shreya Pramanick, Qi Pan, Robert Augustin, Sebastian Bandholtz, William Harriman, Shelley Izquierdo
Raising functional antibodies against G protein-coupled receptors (GPCRs) is challenging due to their low density expression, instability in the absence of the cell membrane's lipid bilayer and frequently short extracellular domains that can serve as antigens. In addition, a particular therapeutic concept may require an antibody to not just bind the receptor, but also act as a functional receptor agonist or antagonist. Antagonizing the glucose-dependent insulinotropic polypeptide (GIP) receptor may open up new therapeutic modalities in the treatment of diabetes and obesity...
January 5, 2017: MAbs
https://www.readbyqxmd.com/read/28055299/guiding-bispecific-monovalent-antibody-formation-through-proteolysis-of-igg1-single-chain
#9
Nazzareno Dimasi, Ryan Fleming, Kris F Sachsenmeier, Binyam Bezabeh, Carl Hay, Jincheng Wu, Erin Sult, Saravanan Rajan, Li Zhuang, Peter Cariuk, Andrew Buchanan, Michael A Bowen, Herren Wu, Changshou Gao
We developed an IgG1 domain-tethering approach to guide the correct assembly of two light and two heavy chains, derived from two different antibodies, to form bispecific monovalent antibodies in IgG1 format. We show here that assembling two different light and heavy chains by sequentially connecting them with protease-cleavable polypeptide linkers results in the generation of monovalent bispecific antibodies that have IgG1 sequence, structure and functional properties. This approach was used to generate a bispecific monovalent antibody targeting the epidermal growth factor receptor and the type I insulin-like growth factor receptor that: 1) can be produced and purified using standard IgG1 techniques; 2) exhibits stability and structural features comparable to IgG1; 3) binds both targets simultaneously; and 4) has potent anti-tumor activity...
January 5, 2017: MAbs
https://www.readbyqxmd.com/read/28055297/a-strategy-to-identify-linker-based-modules-for-the-allosteric-regulation-of-antibody-antigen-binding-affinities-of-different-scfvs
#10
Sarah-Jane Kellmann, Stefan Dübel, Holger Thie
Antibody single-chain variable fragments (scFvs) are used in a variety of applications, such as for research, diagnosis and therapy. Essential for these applications is the extraordinary specificity, selectivity and affinity of antibody paratopes, which can also be employed for efficient protein purification. However, this use is hampered by the high affinity for the protein to be purified because harsh elution conditions, which may impair folding, integrity or viability of the eluted biomaterials, are typically required...
January 5, 2017: MAbs
https://www.readbyqxmd.com/read/28055295/igg-fc-variant-cross-reactivity-between-human-and-rhesus-macaque-fc%C3%AE-rs
#11
Austin W Boesch, Adam R Miles, Ying N Chan, Nana Y Osei-Owusu, Margaret E Ackerman
Non-human primate (NHP) studies are often an essential component of antibody development efforts prior to human trials. Because the efficacy or toxicity of candidate antibodies may depend on their interactions with Fcγ receptors (FcγR) and their resulting ability to induce FcγR-mediated effector functions such as antibody-dependent cell-meditated cytotoxicity and phagocytosis (ADCP), the evaluation of human IgG variants with modulated affinity towards human FcγR is becoming more prevalent in both infectious disease and oncology studies in NHP...
January 5, 2017: MAbs
https://www.readbyqxmd.com/read/27996375/trimeric-gp120-specific-bovine-monoclonal-antibodies-require-cysteine-and-aromatic-residues-in-cdrh3-for-high-affinity-binding-to-hiv-env
#12
Behnaz Heydarchi, Rob J Center, Jonathan Bebbington, Jack Cuthbertson, Christopher Gonelli, Georges Khoury, Charlene Mackenzie, Marit Lichtfuss, Grant Rawlin, Brian Muller, Damian Purcell
We isolated HIV-1 Envelope (Env)-specific memory B cells from a cow that had developed high titre polyclonal immunoglobulin G (IgG) with broad neutralizing activity after a long duration vaccination with HIV-1AD8 Env gp140 trimers. We cloned the bovine IgG matched heavy (H) and light (L) chain variable (V) genes from these memory B cells and constructed IgG monoclonal antibodies (mAbs) with either a human constant (C)-region/bovine V-region chimeric or fully bovine C and V regions. Among 42 selected Ig+ memory B cells, two mAbs (6A and 8C) showed high affinity binding to gp140 Env...
December 20, 2016: MAbs
https://www.readbyqxmd.com/read/28075201/corrigendum
#13
(no author information available yet)
No abstract text is available yet for this article.
February 2017: MAbs
https://www.readbyqxmd.com/read/28071970/the-making-of-bispecific-antibodies
#14
Ulrich Brinkmann, Roland E Kontermann
During the past two decades we have seen a phenomenal evolution of bispecific antibodies for therapeutic applications. The 'zoo' of bispecific antibodies is populated by many different species, comprising around 100 different formats, including small molecules composed solely of the antigen-binding sites of two antibodies, molecules with an IgG structure, and large complex molecules composed of different antigen-binding moieties often combined with dimerization modules. The application of sophisticated molecular design and genetic engineering has solved many of the technical problems associated with the formation of bispecific antibodies such as stability, solubility and other parameters that confer drug properties...
February 2017: MAbs
https://www.readbyqxmd.com/read/28005456/physicochemical-and-biological-characterization-of-sb2-a-biosimilar-of-remicade%C3%A2-infliximab
#15
Juyong Hong, Yuhwa Lee, Changsoo Lee, Suhyeon Eo, Soyeon Kim, Nayoung Lee, Jongmin Park, Seungkyu Park, Donghyuck Seo, Min Jeong, Youngji Lee, Soojeong Yeon, George Bou-Assaf, Zoran Sosic, Wei Zhang, Orlando Jaquez
A biosimilar is a biological medicinal product that contains a version of the active substance of an already authorized original biological medicinal product. Biosimilarity to the reference product (RP) in terms of quality characteristics, such as physicochemical and biological properties, safety, and efficacy, based on a comprehensive comparability exercise needs to be established. SB2 (Flixabi® and Renflexis®) is a biosimilar to Remicade® (infliximab). The development of SB2 was performed in accordance with relevant guidelines of the International Conference on Harmonisation, the European Medicines Agency, and the United States Food and Drug Administration...
February 2017: MAbs
https://www.readbyqxmd.com/read/28001487/impact-of-spr-biosensor-assay-configuration-on-antibody-neonatal-fc-receptor-binding-data
#16
Xiangdan Wang, Patrick McKay, Liliana T Yee, George Dutina, Philip E Hass, Ihsan Nijem, David Allison, Kyra J Cowan, Kevin Lin, Valerie Quarmby, Jihong Yang
Binding interactions with the neonatal Fc receptor (FcRn) are one determinant of pharmacokinetic properties of recombinant human monoclonal antibody (rhumAb) therapeutics, and a conserved binding motif in the crystallizable fragment (Fc) region of IgG molecules interacts with FcRn. Surface plasmon resonance (SPR) biosensor assays are often used to characterize interactions between FcRn and rhumAb therapeutics. In such assays, generally either the rhumAb (format 1) or the FcRn protein (format 2) is immobilized on a biosensor chip...
February 2017: MAbs
https://www.readbyqxmd.com/read/28001485/optimizing-assembly-and-production-of-native-bispecific-antibodies-by-codon-de-optimization
#17
Giovanni Magistrelli, Yves Poitevin, Florence Schlosser, Guillemette Pontini, Pauline Malinge, Soheila Josserand, Marie Corbier, Nicolas Fischer
When production of bispecific antibodies requires the co-expression and assembly of three or four polypeptide chains, low expression of one chain can significantly limit assembly and yield. κλ bodies, fully human bispecific antibodies with native IgG structure, are composed of a common heavy chain and two different light chains, one kappa and one lambda. No engineering is applied to force pairing of the chains, thus both monospecific and bispecific antibodies are secreted in the supernatant. In this context, stoichiometric expression of the two light chains allows for maximal assembly of the bispecific antibody...
February 2017: MAbs
https://www.readbyqxmd.com/read/27981887/insertion-of-scfv-into-the-hinge-domain-of-full-length-igg1-monoclonal-antibody-results-in-tetravalent-bispecific-molecule-with-robust-properties
#18
Binyam Bezabeh, Ryan Fleming, Christine Fazenbaker, Haihong Zhong, Karen Coffman, Xiang-Qing Yu, Ching Ching Leow, Nerea Gibson, Susan Wilson, C Kendall Stover, Herren Wu, Changshou Gao, Nazzareno Dimasi
By simultaneous binding two disease mediators, bispecific antibodies offer the opportunity to broaden the utility of antibody-based therapies. Herein, we describe the design and characterization of Bs4Ab, an innovative and generic bispecific tetravalent antibody platform. The Bs4Ab format comprises a full-length IgG1 monoclonal antibody with a scFv inserted into the hinge domain. The Bs4Ab design demonstrates robust manufacturability as evidenced by MEDI3902, which is currently in clinical development. To further demonstrate the applicability of the Bs4Ab technology, we describe the molecular engineering, biochemical, biophysical, and in vivo characterization of a bispecific tetravalent Bs4Ab that, by simultaneously binding vascular endothelial growth factor and angiopoietin-2, inhibits their function...
February 2017: MAbs
https://www.readbyqxmd.com/read/27981884/quantitative-characterization-of-the-mechanism-of-action-and-impact-of-a-proteolysis-permitting-anti-pcsk9-antibody
#19
Ryan J Hansen, Michael J Berna, Andrea E Sperry, Thomas P Beyer, Victor J Wroblewski, Krista M Schroeder, Patrick I Eacho
A recent report described a novel mechanism of action for an anti-proprotein convertase subtilisin-kexin type 9 (PCSK9) monoclonal antibody (LY3015014, or LY), wherein the antibody has improved potency and duration of action due to the PCSK9 epitope for LY binding. Unlike other antibodies, proteolysis of PCSK9 can occur when LY is bound to PCSK9. We hypothesized that this allowance of PCSK9 cleavage potentially improves LY efficiency through two pathways, namely lack of accumulation of intact PCSK9 and reduced clearance of LY...
February 2017: MAbs
https://www.readbyqxmd.com/read/27960628/antibodies-to-watch-in-2017
#20
Janice M Reichert
Over 50 investigational monoclonal antibody (mAb) therapeutics are currently undergoing evaluation in late-stage clinical studies, which is expected to drive a trend toward first marketing approvals of at least 6-9 mAbs per year in the near-term. In the United States (US), a total of 6 and 9 mAbs were granted first approvals during 2014 and 2015, respectively; all these products are also approved in the European Union (EU). As of December 1, 2016, 6 mAbs (atezolizumab, olaratumab, reslizumab, ixekizumab, bezlotoxumab, oblitoxaximab) had been granted first approvals during 2016 in either the EU or US...
February 2017: MAbs
journal
journal
42089
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"