1,055 results match your criteria mAbs [Journal]


High-throughput retrieval of physical DNA for NGS-identifiable clones in phage display library.

MAbs 2019 Feb 8:1-14. Epub 2019 Feb 8.

a Department of Electrical Engineering and Computer Science , Seoul National University , Seoul , Republic of Korea.

In antibody discovery, in-depth analysis of an antibody library and high-throughput retrieval of clones in the library are crucial to identifying and exploiting rare clones with different properties. However, existing methods have technical limitations, such as low process throughput from the laborious cloning process and waste of the phenotypic screening capacity from unnecessary repetitive tests on the dominant clones. To overcome the limitations, we developed a new high-throughput platform for the identification and retrieval of clones in the library, TrueRepertoire™. Read More

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http://dx.doi.org/10.1080/19420862.2019.1571878DOI Listing
February 2019

Exploring the fate of inhaled monoclonal antibody in the lung parenchyma by microdialysis.

MAbs 2019 Feb/Mar;11(2):297-304. Epub 2019 Feb 4.

a Centre d'Etude des Pathologies Respiratoires , UMR 1100 , INSERM , Tours, France.

Therapeutic antibodies (Abs) are emerging as major drugs to treat respiratory diseases, and inhalation may provide substantial benefits for their delivery. Understanding the behavior of Abs after pulmonary deposition is critical for their development. We investigated the pharmacokinetics of a nebulized Ab by continuous sampling in lung parenchyma using microdialysis in non-human primates. Read More

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http://dx.doi.org/10.1080/19420862.2018.1556081DOI Listing
February 2019

Efficient tumor killing and minimal cytokine release with novel T-cell agonist bispecific antibodies.

MAbs 2019 Jan 30:1-14. Epub 2019 Jan 30.

a Teneobio, Inc ., Menlo Park , CA , USA.

T-cell-recruiting bispecific antibodies (T-BsAbs) have shown potent tumor killing activity in humans, but cytokine release-related toxicities have affected their clinical utility. The use of novel anti-CD3 binding domains with more favorable properties could aid in the creation of T-BsAbs with improved therapeutic windows. Using a sequence-based discovery platform, we identified new anti-CD3 antibodies from humanized rats that bind to multiple epitopes and elicit varying levels of T-cell activation. Read More

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http://dx.doi.org/10.1080/19420862.2019.1574521DOI Listing
January 2019
5 Reads

Rapid production of a chimeric antibody-antigen fusion protein based on 2A-peptide cleavage and green fluorescent protein expression in CHO cells.

MAbs 2019 Jan 29. Epub 2019 Jan 29.

a Laboratory of Immunology, Faculty of Veterinary Medicine , Ughent.

To enable large-scale antibody production, the creation of a stable, high producer cell line is essential. This process often takes longer than 6 months using standard limited dilution techniques and is very labor intensive. The use of a tri-cistronic vector expressing green fluorescent protein (GFP) and both antibody chains, separated by a GT2A peptide sequence, allows expression of all proteins under a single promotor in equimolar ratios. Read More

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http://dx.doi.org/10.1080/19420862.2019.1574531DOI Listing
January 2019
1 Read

Dilute-and-shoot analysis of therapeutic monoclonal antibody variants in fermentation broth: a method capability study.

MAbs 2019 Jan 22:1-14. Epub 2019 Jan 22.

a Department of Biosciences, Bioanalytical Research Labs , University of Salzburg , Salzburg , Austria.

Monoclonal antibodies (mAbs) are widely applied as highly specific and efficient therapeutic agents for various medical conditions, including cancer, inflammatory and autoimmune diseases. As protein production in cellular systems inherently generates a multitude of molecular variants, manufacturing of mAbs requires stringent control in order to ensure safety and efficacy of the drugs. Moreover, monitoring of mAb variants in the course of the fermentation process may allow instant tuning of process parameters to maintain optimal cell culture conditions. Read More

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http://dx.doi.org/10.1080/19420862.2018.1563034DOI Listing
January 2019

ALTHEA Gold Libraries™: Antibody libraries for therapeutic antibody discovery.

MAbs 2019 Jan 20. Epub 2019 Jan 20.

d GlobalBio, Inc ., Cambridge , MA , USA.

We describe here the design, construction and validation of ALTHEA Gold Libraries™. These single-chain variable fragment, semisynthetic libraries are built on synthetic human well-known IGHV and IGKV germline genes combined with natural human complementarity-determining region (CDR)-H3/J (H3J) fragments. One IGHV gene provided a universal V scaffold and was paired with two IGKV scaffolds to furnish different topographies for binding distinct epitopes. Read More

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http://dx.doi.org/10.1080/19420862.2019.1571879DOI Listing
January 2019
2 Reads

Covalent labeling and mass spectrometry reveal subtle higher order structural changes for antibody therapeutics.

MAbs 2019 Jan 13:1-14. Epub 2019 Jan 13.

a Department of Chemistry , University of Massachusetts Amherst , Amherst , MA , USA.

Monoclonal antibodies are among the fastest growing therapeutics in the pharmaceutical industry. Detecting higher-order structure changes of antibodies upon storage or mishandling, however, is a challenging problem. In this study, we describe the use of diethylpyrocarbonate (DEPC)-based covalent labeling (CL) - mass spectrometry (MS) to detect conformational changes caused by heat stress, using rituximab as a model system. Read More

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http://dx.doi.org/10.1080/19420862.2019.1565748DOI Listing
January 2019

A general platform for antibody purification utilizing engineered-micelles.

MAbs 2019 Jan 8:1-10. Epub 2019 Jan 8.

a Department of Chemical Sciences , Ariel University , Ariel , Israel.

We introduce a new concept and potentially general platform for antibody (Ab) purification that does not rely on chromatography or specific ligands (e.g., Protein A); rather, it makes use of detergent aggregates capable of efficiently capturing Ab while rejecting hydrophilic impurities. Read More

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http://dx.doi.org/10.1080/19420862.2019.1565749DOI Listing
January 2019
5 Reads
4.558 Impact Factor

A recycling anti-transferrin receptor-1 monoclonal antibody as an efficient therapy for erythroleukemia through target up-regulation and antibody-dependent cytotoxic effector functions.

MAbs 2019 Jan 3:1-13. Epub 2019 Jan 3.

a IRCM, Institut de Recherche en Cancérologie de Montpellier ; INSERM, U1194, Université de Montpellier, Montpellier , France.

Targeting transferrin receptor 1 (TfR1) with monoclonal antibodies is a promising therapeutic strategy in cancer as tumor cells often overexpress TfR1 and show increased iron needs. We have re-engineered six anti-human TfR1 single-chain variable fragment (scFv) antibodies into fully human scFv-Fcγ1 and IgG1 antibodies. We selected the more promising candidate (H7), based on its ability to inhibit TfR1-mediated iron-loaded transferrin internalization in Raji cells (B-cell lymphoma). Read More

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http://dx.doi.org/10.1080/19420862.2018.1564510DOI Listing
January 2019
5 Reads

Modulating cell culture oxidative stress reduces protein glycation and acidic charge variant formation.

MAbs 2019 Jan 3;11(1):205-216. Epub 2019 Jan 3.

b Biologics Development, Global Product Development and Supply , Bristol-Myers Squibb Company , Devens , MA.

Controlling acidic charge variants is critical for an industrial bioprocess due to the potential impact on therapeutic efficacy and safety. Achieving a consistent charge variant profile at manufacturing scale remains challenging and may require substantial resources to investigate effective control strategies. This is partially due to incomplete understanding of the underlying causes for charge variant formation during the cell culture process. Read More

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http://dx.doi.org/10.1080/19420862.2018.1537533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343810PMC
January 2019

Enabling adoption of 2D-NMR for the higher order structure assessment of monoclonal antibody therapeutics.

MAbs 2019 Jan 22;11(1):94-105. Epub 2018 Dec 22.

ad Higher Order Structure, Attribute Sciences , Amgen Inc ., Thousand Oaks , CA , USA.

The increased interest in using monoclonal antibodies (mAbs) as a platform for biopharmaceuticals has led to the need for new analytical techniques that can precisely assess physicochemical properties of these large and very complex drugs for the purpose of correctly identifying quality attributes (QA). One QA, higher order structure (HOS), is unique to biopharmaceuticals and essential for establishing consistency in biopharmaceutical manufacturing, detecting process-related variations from manufacturing changes and establishing comparability between biologic products. To address this measurement challenge, two-dimensional nuclear magnetic resonance spectroscopy (2D-NMR) methods were introduced that allow for the precise atomic-level comparison of the HOS between two proteins, including mAbs. Read More

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http://dx.doi.org/10.1080/19420862.2018.1544454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343768PMC
January 2019
3 Reads
4.558 Impact Factor

Co-engaging CD47 and CD19 with a bispecific antibody abrogates B-cell receptor/CD19 association leading to impaired B-cell proliferation.

MAbs 2019 Feb/Mar;11(2):322-334. Epub 2019 Jan 31.

a Exploratory Sciences , NovImmune SA , Plan les Ouates , Switzerland.

CD19 is a B cell-specific receptor that regulates the threshold of B cell receptor (BCR)-mediated cell proliferation. A CD47xCD19 bispecific antibody (biAb) was generated to target and deplete B cells via multiple antibody-mediated mechanisms. Interestingly, the biAb, constructed of a CD19 binding arm and a CD47 binding arm, inhibited BCR-mediated B-cell proliferation with an effect even more potent than a CD19 monoclonal antibody (mAb). Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2018.1
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http://dx.doi.org/10.1080/19420862.2018.1558698DOI Listing
January 2019
4 Reads

De novo generation of specific human IgGs by in vitro immunization using autologous proteins containing immunogenic p-nitrophenylalanine.

MAbs 2019 Feb/Mar;11(2):401-410. Epub 2018 Dec 22.

a Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology , China Pharmaceutical University , Nanjing , China.

In vitro immunization can to used to produce monoclonal antibodies(mAbs), but this technology is limited by poor reproducibility and the requirement of pre-immunized lymphocytes. To improve this approach, we recently developed a method for rapid generation of antigen-specific B cells. Here, we report the application of this system to the production of human IgGs against tumor necrosis factor (TNF). Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2018.1
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http://dx.doi.org/10.1080/19420862.2018.1537580DOI Listing
December 2018
1 Read

Single cell-produced and in vitro-assembled anti-FcRH5/CD3 T-cell dependent bispecific antibodies have similar in vitro and in vivo properties.

MAbs 2019 Feb/Mar;11(2):422-433. Epub 2018 Dec 17.

a Genentech Research and Early Development, Genentech, Inc ., South San Francisco , CA , USA.

Bispecific antibody production using single host cells has been a new advancement in the antibody engineering field. We previously showed comparable in vitro biological activity and in vivo mouse pharmacokinetics (PK) for two novel single cell variants (v10 and v11) and one traditional dual cell in vitro-assembled anti-human epidermal growth factor receptor 2/CD3 T-cell dependent bispecific (TDB) antibodies. Here, we extended our previous work to assess single cell-produced bispecific variants of a novel TDB against FcRH5, a B-cell lineage marker expressed on multiple myeloma (MM) tumor cells. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2018.1
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http://dx.doi.org/10.1080/19420862.2018.1551676DOI Listing
December 2018
1 Read

Structure, heterogeneity and developability assessment of therapeutic antibodies.

MAbs 2019 Feb/Mar;11(2):239-264. Epub 2018 Dec 17.

c Product Characterization , Alexion Pharmaceuticals, Inc ., New Haven , CT , USA.

Increasing attention has been paid to developability assessment with the understanding that thorough evaluation of monoclonal antibody lead candidates at an early stage can avoid delays during late-stage development. The concept of developability is based on the knowledge gained from the successful development of approximately 80 marketed antibody and Fc-fusion protein drug products and from the lessons learned from many failed development programs over the last three decades. Here, we reviewed antibody quality attributes that are critical to development and traditional and state-of-the-art analytical methods to monitor those attributes. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2018.1
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http://dx.doi.org/10.1080/19420862.2018.1553476DOI Listing
December 2018
14 Reads

Anti-PD1 'SHR-1210' aberrantly targets pro-angiogenic receptors and this polyspecificity can be ablated by paratope refinement.

MAbs 2019 Jan 12;11(1):26-44. Epub 2018 Dec 12.

a UltraHuman Limited, Codebase , Edinburgh , UK.

Monoclonal anti-programmed cell death 1 (PD1) antibodies are successful cancer therapeutics, but it is not well understood why individual antibodies should have idiosyncratic side-effects. As the humanized antibody SHR-1210 causes capillary hemangioma in patients, a unique toxicity amongst anti-PD1 antibodies, we performed human receptor proteome screening to identify nonspecific interactions that might drive angiogenesis. This screen identified that SHR-1210 mediated aberrant, but highly selective, low affinity binding to human receptors such as vascular endothelial growth factor receptor 2 (VEGFR2), frizzled class receptor 5 and UL16 binding protein 2 (ULBP2). Read More

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http://dx.doi.org/10.1080/19420862.2018.1550321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343799PMC
January 2019
17 Reads

In vitro and in silico assessment of the developability of a designed monoclonal antibody library.

MAbs 2019 Feb/Mar;11(2):388-400. Epub 2019 Jan 18.

a Large Protein Biophysics , Novo Nordisk A/S , Måløv , Denmark.

Despite major advances in antibody discovery technologies, the successful development of monoclonal antibodies (mAbs) into effective therapeutic and diagnostic agents can often be impeded by developability liabilities, such as poor expression, low solubility, high viscosity and aggregation. Therefore, strategies to predict at the early phases of antibody development the risk of late-stage failure of antibody candidates are highly valuable. In this work, we employ the in silico solubility predictor CamSol to design a library of 17 variants of a humanized mAb predicted to span a broad range of solubility values, and we examine their developability potential with a battery of commonly used in vitro and in silico assays. Read More

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http://dx.doi.org/10.1080/19420862.2018.1556082DOI Listing
January 2019

Ion channels as therapeutic antibody targets.

MAbs 2019 Feb/Mar;11(2):265-296. Epub 2018 Dec 10.

a TetraGenetics Inc , Arlington Massachusetts , USA.

It is now well established that antibodies have numerous potential benefits when developed as therapeutics. Here, we evaluate the technical challenges of raising antibodies to membrane-spanning proteins together with enabling technologies that may facilitate the discovery of antibody therapeutics to ion channels. Additionally, we discuss the potential targeting opportunities in the anti-ion channel antibody landscape, along with a number of case studies where functional antibodies that target ion channels have been reported. Read More

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http://dx.doi.org/10.1080/19420862.2018.1548232DOI Listing
December 2018
1 Read

Engineered pH-dependent recycling antibodies enhance elimination of Staphylococcal enterotoxin B superantigen in mice.

MAbs 2019 Feb/Mar;11(2):411-421. Epub 2018 Dec 11.

a Department of Chemical and Biological Engineering , University at Buffalo , Buffalo , New York , USA.

A new modality in antibody engineering has emerged in which the antigen affinity is designed to be pH dependent (PHD). In particular, combining high affinity binding at neutral pH with low affinity binding at acidic pH leads to a novel antibody that can more effectively neutralize the target antigen while avoiding antibody-mediated antigen accumulation. Here, we studied how the in vivo pharmacokinetics of the superantigen, Staphylococcal enterotoxin B (SEB), is affected by an engineered antibody with pH-dependent binding. Read More

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http://dx.doi.org/10.1080/19420862.2018.1545510DOI Listing
December 2018
1 Read

Effective binding to protein antigens by antibodies from antibody libraries designed with enhanced protein recognition propensities.

MAbs 2019 Feb/Mar;11(2):373-387. Epub 2019 Jan 9.

a Genomics Research Center , Academia Sinica , Taipei , Taiwan.

Antibodies provide immune protection by recognizing antigens of diverse chemical properties, but elucidating the amino acid sequence-function relationships underlying the specificity and affinity of antibody-antigen interactions remains challenging. We designed and constructed phage-displayed synthetic antibody libraries with enriched protein antigen-recognition propensities calculated with machine learning predictors, which indicated that the designed single-chain variable fragment variants were encoded with enhanced distributions of complementarity-determining region (CDR) hot spot residues with high protein antigen recognition propensities in comparison with those in the human antibody germline sequences. Antibodies derived directly from the synthetic antibody libraries, without affinity maturation cycles comparable to those in in vivo immune systems, bound to the corresponding protein antigen through diverse conformational or linear epitopes with specificity and affinity comparable to those of the affinity-matured antibodies from in vivo immune systems. Read More

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http://dx.doi.org/10.1080/19420862.2018.1550320DOI Listing
January 2019
4.558 Impact Factor

Deamidation and isomerization liability analysis of 131 clinical-stage antibodies.

MAbs 2019 Jan 10;11(1):45-57. Epub 2018 Dec 10.

a Protein Analytics , Adimab , Lebanon , NH , USA.

Contemporary in vivo and in vitro discovery platform technologies greatly increase the odds of identifying high-affinity monoclonal antibodies (mAbs) towards essentially any desired biologically relevant epitope. Lagging discovery throughput is the ability to select for highly developable mAbs with drug-like properties early in the process. Upstream consideration of developability metrics should reduce the frequency of failures in later development stages. Read More

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http://dx.doi.org/10.1080/19420862.2018.1548233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343770PMC
January 2019

Generation by phage display and characterization of drug-target complex-specific antibodies for pharmacokinetic analysis of biotherapeutics.

MAbs 2019 Jan 5;11(1):178-190. Epub 2018 Dec 5.

a Bio-Rad, Antibody Division , Puchheim , Germany.

Anti-idiotypic antibodies play an important role in pre-clinical and clinical development of therapeutic antibodies, where they are used for pharmacokinetic studies and for the development of immunogenicity assays. By using an antibody phage display library in combination with guided in vitro selection against various marketed drugs, we generated antibodies that recognize the drug only when bound to its target. We have named such specificities Type 3, to distinguish them from the anti-idiotypic antibodies that specifically detect free antibody drug or total drug. Read More

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http://dx.doi.org/10.1080/19420862.2018.1538723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343800PMC
January 2019
2 Reads

Antibodies to watch in 2019.

MAbs 2019 Feb/Mar;11(2):219-238. Epub 2018 Dec 22.

b The Antibody Society , Framingham , MA , USA.

For the past 10 years, the annual 'Antibodies to watch' articles have provided updates on key events in the late-stage development of antibody therapeutics, such as first regulatory review or approval, that occurred in the year before publication or were anticipated to occur during the year of publication. To commemorate the 10th anniversary of the article series and to celebrate the 2018 Nobel Prizes in Chemistry and in Physiology or Medicine, which were given for work that is highly relevant to antibody therapeutics research and development, we expanded the scope of the data presented to include an overview of all commercial clinical development of antibody therapeutics and approval success rates for this class of molecules. Our data indicate that: 1) antibody therapeutics are entering clinical study, and being approved, in record numbers; 2) the commercial pipeline is robust, with over 570 antibody therapeutics at various clinical phases, including 62 in late-stage clinical studies; and 3) Phase 1 to approval success rates are favorable, ranging from 17-25%, depending on the therapeutic area (cancer vs. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2018.1
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http://dx.doi.org/10.1080/19420862.2018.1556465DOI Listing
December 2018
27 Reads

C2 domain orientation of human immunoglobulin G in solution: Structural comparison of glycosylated and aglycosylated Fc regions using small-angle X-ray scattering.

MAbs 2018 Dec 4. Epub 2018 Dec 4.

a Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences , the University of Tokyo , Kashiwa , Chiba , Japan.

The N-linked glycan in immunoglobulin G is critical for the stability and function of the crystallizable fragment (Fc) region. Alteration of these protein properties upon the removal of the N-linked glycan has often been explained by the alteration of the C2 domain orientation in the Fc region. To confirm this hypothesis, we examined the small-angle X-ray scattering (SAXS) profile of the glycosylated Fc region (gFc) and aglycosylated Fc region (aFc) in solution. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2018.1
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http://dx.doi.org/10.1080/19420862.2018.1546086DOI Listing
December 2018
30 Reads

Influence of N-glycosylation on effector functions and thermal stability of glycoengineered IgG1 monoclonal antibody with homogeneous glycoforms.

MAbs 2019 Feb/Mar;11(2):350-372. Epub 2018 Dec 10.

b Department of Medical Life Science, Graduate School of Medical Life Science , Yokohama City University , Tsurumi , Yokohama , Japan.

Glycosylation of the conserved asparagine residue in each heavy chain of IgG in the CH2 domain is known as N-glycosylation. It is one of the most common post-translational modifications and important critical quality attributes of monoclonal antibody (mAb) therapeutics. Various studies have demonstrated the effects of the Fc N-glycosylation on safety, Fc effector functions, and pharmacokinetics, both dependent and independent of neonatal Fc receptor (FcRn) pathway. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2018.1
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http://dx.doi.org/10.1080/19420862.2018.1551044DOI Listing
December 2018
6 Reads

Nanobodies reveal an extra-synaptic population of SNAP-25 and Syntaxin 1A in hippocampal neurons.

MAbs 2019 Feb/Mar;11(2):305-321. Epub 2018 Dec 28.

a Institute of Neuro- and Sensory Physiology , University Medical Center Göttingen , Göttingen , Germany.

Synaptic vesicle fusion (exocytosis) is a precisely regulated process that entails the formation of SNARE complexes between the vesicle protein synaptobrevin 2 (VAMP2) and the plasma membrane proteins Syntaxin 1 and SNAP-25. The sub-cellular localization of the latter two molecules remains unclear, although they have been the subject of many recent investigations. To address this, we generated two novel camelid single domain antibodies (nanobodies) specifically binding to SNAP-25 and Syntaxin 1A. Read More

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http://dx.doi.org/10.1080/19420862.2018.1551675DOI Listing
December 2018
2 Reads

Correction.

Authors:

MAbs 2018 Nov 13. Epub 2018 Nov 13.

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http://dx.doi.org/10.1080/19420862.2018.1546991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343788PMC
November 2018
1 Read

The first World Health Organization International Standard for infliximab products: A step towards maintaining harmonized biological activity.

MAbs 2019 Jan 5;11(1):13-25. Epub 2018 Nov 5.

a Division of Biotherapeutics , National Institute for Biological Standards and Control (NIBSC) , South Mimms , Potters Bar, Hertfordshire , UK.

Due to the increase in the number of infliximab products, the need for global harmonization of the bioactivity of this monoclonal antibody was recognized by the World Health Organization (WHO). In response, the National Institute for Biological Standards and Control (NIBSC) developed the first international standard (IS) for infliximab, which targets tumour necrosis factor (TNF). Each ampoule is assigned values of 500 IU of TNF neutralizing activity and 500 IU of binding activity. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2018.1
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http://dx.doi.org/10.1080/19420862.2018.1532766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343779PMC
January 2019
20 Reads

Antibody-drug conjugates with HER2-targeting antibodies from synthetic antibody libraries are highly potent against HER2-positive human gastric tumor in xenograft models.

MAbs 2019 Jan 8;11(1):153-165. Epub 2018 Nov 8.

a Genomics Research Center , Academia Sinica , Taipei , Taiwan.

HER2-ECD (human epidermal growth factor receptor 2 - extracellular domain) is a prominent therapeutic target validated for treating HER2-positive breast and gastric cancer, but HER2-specific therapeutic options for treating advanced gastric cancer remain limited. We have developed antibody-drug conjugates (ADCs), comprising IgG1 linked via valine-citrulline to monomethyl auristatin E, with potential to treat HER2-positive gastric cancer in humans. The antibodies optimally selected from the ADC discovery platform, which was developed to discover antibody candidates suitable for immunoconjugates from synthetic antibody libraries designed using antibody-antigen interaction principles, were demonstrated to be superior immunoconjugate targeting modules in terms of efficacy and off-target toxicity. Read More

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http://dx.doi.org/10.1080/19420862.2018.1541370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343809PMC
January 2019
20 Reads
4.560 Impact Factor

Expression vector-derived heterogeneity in a therapeutic IgG4 monoclonal antibody.

MAbs 2019 Jan 7;11(1):145-152. Epub 2018 Nov 7.

a Biologics Analytical Operations , Gilead Sciences , Oceanside , CA , USA.

While characterizing a therapeutic IgG4 monoclonal antibody (mAb), we observed a variant with a mass 1177 Da larger than the predominant mAb form that could not be ascribed to previously described modifications. Through successive rounds of experimentation, we localized the mass addition to the C-terminus of the heavy chain (HC). During this process we observed that when the mAb was broken down into separate domains, the Fc and the 1177 Da-modified Fc could be chromatographically separated. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2018.1
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http://dx.doi.org/10.1080/19420862.2018.1540254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343794PMC
January 2019
11 Reads

Charge variant native mass spectrometry benefits mass precision and dynamic range of monoclonal antibody intact mass analysis.

MAbs 2018 Nov-Dec;10(8):1214-1225. Epub 2018 Oct 19.

b Department of Microchemistry, Proteomics and Lipidomics , Genentech, Inc , South San Francisco , CA , USA.

The preponderance and diversity of charge variants in therapeutic monoclonal antibodies has implications for antibody efficacy and degradation. Understanding the extent and impact of minor antibody variants is of great interest, and it is also a critical regulatory requirement. Traditionally, a combination of approaches is used to characterize antibody charge heterogeneity, including ion exchange chromatography and independent mass spectrometric variant site mapping after proteolytic digestion. Read More

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http://dx.doi.org/10.1080/19420862.2018.1521131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284562PMC
October 2018
1 Read
4.560 Impact Factor

Evidence of disulfide bond scrambling during production of an antibody-drug conjugate.

MAbs 2018 Nov-Dec;10(8):1190-1199. Epub 2018 Oct 19.

a Analytical and Formulation Development , Agensys, Inc., an affiliate of Astellas, Inc , Santa Monica , CA , USA.

Antibody-drug conjugates (ADCs) that are formed using thiol-maleimide chemistry are commonly produced by reactions that occur at or above neutral pHs. Alkaline environments can promote disulfide bond scrambling, and may result in the reconfiguration of interchain disulfide bonds in IgG antibodies, particularly in the IgG2 and IgG4 subclasses. IgG2-A and IgG2-B antibodies generated under basic conditions yielded ADCs with comparable average drug-to-antibody ratios and conjugate distributions. Read More

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http://dx.doi.org/10.1080/19420862.2018.1521128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284598PMC
October 2018

High-resolution glycosylation site-engineering method identifies MICA epitope critical for shedding inhibition activity of anti-MICA antibodies.

MAbs 2019 Jan 22;11(1):75-93. Epub 2018 Nov 22.

a Department of Antibody Engineering , Genentech Inc ., South San Francisco , USA.

As an immune evasion strategy, MICA and MICB, the major histocompatibility complex class I homologs, are proteolytically cleaved from the surface of cancer cells leading to impairment of CD8 + T cell- and natural killer cell-mediated immune responses. Antibodies that inhibit MICA/B shedding from tumors have therapeutic potential, but the optimal epitopes are unknown. Therefore, we developed a high-resolution, high-throughput glycosylation-engineered epitope mapping (GEM) method, which utilizes site-specific insertion of N-linked glycans onto the antigen surface to mask local regions. Read More

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http://dx.doi.org/10.1080/19420862.2018.1532767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343778PMC
January 2019
3 Reads

Evolution of a comprehensive, orthogonal approach to sequence variant analysis for biotherapeutics.

MAbs 2019 Jan 25;11(1):1-12. Epub 2018 Oct 25.

a Biotherapeutics Pharmaceutical Sciences , Pfizer, Inc , Andover , MA , USA.

Amino acid sequence variation in protein therapeutics requires close monitoring during cell line and cell culture process development. A cross-functional team of Pfizer colleagues from the Analytical and Bioprocess Development departments worked closely together for over 6 years to formulate and communicate a practical, reliable sequence variant (SV) testing strategy with state-of-the-art techniques that did not necessitate more resources or lengthen project timelines. The final Pfizer SV screening strategy relies on next-generation sequencing (NGS) and amino acid analysis (AAA) as frontline techniques to identify mammalian cell clones with genetic mutations and recognize cell culture process media/feed conditions that induce misincorporations, respectively. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2018.1
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http://dx.doi.org/10.1080/19420862.2018.1531965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343769PMC
January 2019
16 Reads

Comprehensive characterisation of the heterogeneity of adalimumab via charge variant analysis hyphenated on-line to native high resolution Orbitrap mass spectrometry.

MAbs 2019 Jan 11;11(1):116-128. Epub 2018 Nov 11.

a Characterisation and Comparability Lab , NIBRT - The National Institute for Bioprocessing Research and Training , Co , Dublin , Ireland.

Charge variant analysis is a widely used tool to monitor changes in product quality during the manufacturing process of monoclonal antibodies (mAbs). Although it is a powerful technique for revealing mAb heterogeneity, an unexpected outcome, for example the appearance of previously undetected isoforms, requires further, time-consuming analysis. The process of identifying these unknowns can also result in unwanted changes to the molecule that are not attributable to the manufacturing process. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2018.1
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http://dx.doi.org/10.1080/19420862.2018.1531664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343805PMC
January 2019
4 Reads

Evaluation of similar quality attribute characteristics in SB5 and reference product of adalimumab.

MAbs 2019 Jan 19;11(1):129-144. Epub 2018 Oct 19.

b Bioanalysis Team , Samsung Bioepis Co., Ltd ., Incheon , South Korea.

Biosimilars are biologic products that are highly similar to a licensed reference product in terms of quality, safety, and efficacy. SB5 is a biosimilar of Humira® (adalimumab) developed by Samsung Bioepis. To demonstrate its biosimilarity in quality to Humira®, we performed a comprehensive characterization in terms of structure, physicochemical properties, and biological properties following the International Conference on Harmonization, US Food and Drug Administration, and European Medicines Agency guidelines. Read More

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http://dx.doi.org/10.1080/19420862.2018.1530920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343792PMC
January 2019
2 Reads

Rapid, automated characterization of disulfide bond scrambling and IgG2 isoform determination.

MAbs 2018 Nov-Dec;10(8):1200-1213. Epub 2018 Oct 2.

a BioPharma Solutions R&D , BALS, Bruker Daltonik , Bremen , Germany.

Human antibodies of the IgG2 subclass exhibit complex inter-chain disulfide bonding patterns that result in three structures, namely A, A/B, and B. In therapeutic applications, the distribution of disulfide isoforms is a critical product quality attribute because each configuration affects higher order structure, stability, isoelectric point, and antigen binding. The current standard for quantification of IgG2 disulfide isoform distribution is based on chromatographic or electrophoretic techniques that require additional characterization using mass spectrometry (MS)-based methods to confirm disulfide linkages. Read More

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http://dx.doi.org/10.1080/19420862.2018.1512328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284591PMC
October 2018
19 Reads

Antibody-drug conjugate library prepared by scanning insertion of the aldehyde tag into IgG1 constant regions.

MAbs 2018 Nov-Dec;10(8):1182-1189. Epub 2018 Sep 25.

a Catalent Biologics , Emeryville , CA , USA.

The advantages of site-specific over stochastic bioconjugation technologies include homogeneity of product, minimal perturbation of protein structure/function, and - increasingly - the ability to perform structure activity relationship studies at the conjugate level. When selecting the optimal location for site-specific payload placement, many researchers turn to in silico modeling of protein structure to identify regions predicted to offer solvent-exposed conjugatable sites while conserving protein function. Here, using the aldehyde tag as our site-specific technology platform and human IgG1 antibody as our target protein, we demonstrate the power of taking an unbiased scanning approach instead. Read More

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http://dx.doi.org/10.1080/19420862.2018.1512327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284588PMC
September 2018
8 Reads

Prediction of methionine oxidation risk in monoclonal antibodies using a machine learning method.

MAbs 2018 Nov-Dec;10(8):1281-1290. Epub 2018 Sep 25.

a Department of Antibody Engineering , Genentech , South San Francisco , CA , USA.

Monoclonal antibodies (mAbs) have become a major class of protein therapeutics that target a spectrum of diseases ranging from cancers to infectious diseases. Similar to any protein molecule, mAbs are susceptible to chemical modifications during the manufacturing process, long-term storage, and in vivo circulation that can impair their potency. One such modification is the oxidation of methionine residues. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2018.1
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http://dx.doi.org/10.1080/19420862.2018.1518887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284603PMC
September 2018
40 Reads

Monovalent TNF receptor 1-selective antibody with improved affinity and neutralizing activity.

MAbs 2019 Jan 2;11(1):166-177. Epub 2018 Oct 2.

a Institute of Cell Biology and Immunology , University of Stuttgart , Stuttgart , Germany.

Selective inhibition of tumor necrosis factor (TNF) signaling through the proinflammatory axis of TNF-receptor 1 (TNFR1) while leaving pro-survival and regeneration-promoting signals via TNFR2 unaffected is a promising strategy to circumvent limitations of complete inhibition of TNF action by the approved anti-TNF drugs. A previously developed humanized antagonistic TNFR1-specific antibody, ATROSAB, showed potent inhibition of TNFR1-mediated cellular responses. Because the parental mouse antibody H398 possesses even stronger inhibitory potential, we scrutinized the specific binding parameters of the two molecules and revealed a faster dissociation of ATROSAB compared to H398. Read More

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http://dx.doi.org/10.1080/19420862.2018.1524664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343807PMC
January 2019
1 Read

Comprehensive manipulation of glycosylation profiles across development scales.

MAbs 2019 Feb/Mar;11(2):335-349. Epub 2018 Oct 22.

b Technical Operations , ImmunoGen, Waltham , USA.

The extent and pattern of glycosylation on therapeutic antibodies can influence their circulatory half-life, engagement of effector functions, and immunogenicity, with direct consequences to efficacy and patient safety. Hence, controlling glycosylation patterns is central to any drug development program, yet poses a formidable challenge to the bio-manufacturing industry. Process changes, which can affect glycosylation patterns, range from manufacturing at different scales or sites, to switching production process mode, all the way to using alternative host cell lines. Read More

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http://dx.doi.org/10.1080/19420862.2018.1527665DOI Listing
October 2018
12 Reads

Systematic development of temperature shift strategies for Chinese hamster ovary cells based on short duration cultures and kinetic modeling.

MAbs 2019 Jan 2;11(1):191-204. Epub 2018 Oct 2.

a Global Product Development and Supply , Bristol-Myers Squibb Company , Devens , MA , USA.

Temperature shift (TS) to a hypothermic condition has been widely used during protein production processes that use Chinese hamster ovary (CHO) cells. The effect of temperature on cell growth, metabolites, protein titer and quality depends on cell line, product, and other bioreactor conditions. Due to the large numbers of experiments, which typically last 2-3 weeks each, limited systematic TS studies have been reported with multiple shift temperatures and steps at different times. Read More

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http://dx.doi.org/10.1080/19420862.2018.1525262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343780PMC
January 2019
1 Read

Comprehensive characterization of monoclonal antibody by Fourier transform ion cyclotron resonance mass spectrometry.

MAbs 2019 Jan 22;11(1):106-115. Epub 2018 Dec 22.

a Department of Chemistry , University of Wisconsin-Madison , Madison , Wisconsin , USA.

The pharmaceutical industry's interest in monoclonal antibodies (mAbs) and their derivatives has spurred rapid growth in the commercial and clinical pipeline of these effective therapeutics. The complex micro-heterogeneity of mAbs requires in-depth structural characterization for critical quality attribute assessment and quality assurance. Currently, mass spectrometry (MS)-based methods are the gold standard in mAb analysis, primarily with a bottom-up approach in which immunoglobulins G (IgGs) and their variants are digested into peptides to facilitate the analysis. Read More

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http://dx.doi.org/10.1080/19420862.2018.1525253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343775PMC
January 2019

EFab domain substitution as a solution to the light-chain pairing problem of bispecific antibodies.

MAbs 2018 Nov-Dec;10(8):1248-1259. Epub 2018 Sep 20.

a Department of Biotherapeutic and Medicinal Sciences , Biogen , Cambridge , MA , USA.

Bispecific antibody therapeutics can expand the functionality of a conventional monoclonal antibody drug because they can bind multiple antigens. However, their great potential is counterbalanced by the challenges faced in their production. The classic asymmetric bispecific containing an Fc requires the expression of four unique chains - two light chains and two heavy chains; each light chain must pair with its correct heavy chain, which then must heterodimerize to form the full bispecific. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2018.1
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http://dx.doi.org/10.1080/19420862.2018.1519631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284599PMC
September 2018
7 Reads

Antigen binding allosterically promotes Fc receptor recognition.

MAbs 2019 Jan 5;11(1):58-74. Epub 2018 Oct 5.

b Basic Science Program , Leidos Biomedical Research, Inc., Cancer and Inflammation Program, National Cancer Institute , Frederick , Maryland , USA.

A key question in immunology is whether antigen recognition and Fc receptor (FcR) binding are allosterically linked. This question is also relevant for therapeutic antibody design. Antibody Fab and Fc domains are connected by flexible unstructured hinge region. Read More

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http://dx.doi.org/10.1080/19420862.2018.1522178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343797PMC
January 2019
3 Reads

Establishment of peripheral blood mononuclear cell-derived humanized lung cancer mouse models for studying efficacy of PD-L1/PD-1 targeted immunotherapy.

MAbs 2018 Nov-Dec;10(8):1301-1311. Epub 2018 Oct 2.

b Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine , Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou , China.

Animal models used to evaluate efficacies of immune checkpoint inhibitors are insufficient or inaccurate. We thus examined two xenograft models used for this purpose, with the aim of optimizing them. One method involves the use of peripheral blood mononuclear cells and cell line-derived xenografts (PBMCs-CDX model). Read More

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http://dx.doi.org/10.1080/19420862.2018.1518948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284590PMC
October 2018
4 Reads
4.560 Impact Factor

MHC-associated peptide proteomics enabling highly sensitive detection of immunogenic sequences for the development of therapeutic antibodies with low immunogenicity.

MAbs 2018 Nov-Dec;10(8):1168-1181. Epub 2018 Oct 1.

a Research Division, Fuji Gotemba Research Labs , Chugai Pharmaceutical Co., Ltd ., Gotemba , Shizuoka , Japan.

Immunogenicity is a key factor capable of influencing the efficacy and safety of therapeutic antibodies. A recently developed method called MHC-associated peptide proteomics (MAPPs) uses liquid chromatography/mass spectrometry to identify the peptide sequences derived from a therapeutic protein that are presented by major histocompatibility complex class II (MHC II) on antigen-presenting cells, and therefore may induce immunogenicity. In this study, we developed a MAPPs technique (called Ab-MAPPs) that has high throughput and can efficiently identify the MHC II-presented peptides derived from therapeutic antibodies using magnetic nanoparticle beads coated with a hydrophilic polymer in the immunoprecipitation process. Read More

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http://dx.doi.org/10.1080/19420862.2018.1518888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284561PMC
October 2018
1 Read

Site-specific conjugation allows modulation of click reaction stoichiometry for pretargeted SPECT imaging.

MAbs 2018 Nov-Dec;10(8):1269-1280. Epub 2018 Oct 4.

a Preclinical and Translational Pharmacokinetics , Genentech Inc ., South San Francisco , CA , USA.

Antibody pretargeting is a promising strategy for improving molecular imaging, wherein the separation in time of antibody targeting and radiolabeling can lead to rapid attainment of high contrast, potentially increased sensitivity, and reduced patient radiation exposure. The inverse electron demand Diels-Alder 'click' reaction between trans-cyclooctene (TCO) conjugated antibodies and radiolabeled tetrazines presents an ideal platform for pretargeted imaging due to rapid reaction kinetics, bioorthogonality, and potential for optimization of both slow and fast clearing components. Herein, we evaluated a series of anti-human epidermal growth factor receptor 2 (HER2) pretargeting antibodies containing distinct molar ratios of site-specifically incorporated TCO. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2018.1
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http://dx.doi.org/10.1080/19420862.2018.1521132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284555PMC
October 2018
5 Reads

Non-neutralizing antibodies increase endogenous circulating Ang1 levels.

MAbs 2018 Nov-Dec;10(8):1260-1268. Epub 2018 Nov 7.

a Biotherapeutics Discovery Research , Boehringer Ingelheim Parmaceuticals, Inc , Ridgefield , Connecticut , USA.

Ang1 is a soluble ligand to receptor Tie2, and increasing the circulating Ang1 level may improve vascular stabilization under certain disease conditions. Here, we found that the circulating Ang1 level was significantly increased in cynomolgus monkeys treated with non-neutralizing anti-Ang1 antibodies. Improving the antibodies' pharmacokinetic properties by IgG Fc mutations further increased the circulating Ang1 level. Read More

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http://dx.doi.org/10.1080/19420862.2018.1521130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284558PMC
November 2018
10 Reads

A synthetic anti-Frizzled antibody engineered for broadened specificity exhibits enhanced anti-tumor properties.

MAbs 2018 Nov-Dec;10(8):1157-1167. Epub 2018 Sep 25.

a Terrence Donnelly Centre for Cellular and Biomolecular Research , University of Toronto , Toronto , Canada.

Secreted Wnt ligands play a major role in the development and progression of many cancers by modulating signaling through cell-surface Frizzled receptors (FZDs). In order to achieve maximal effect on Wnt signaling by targeting the cell surface, we developed a synthetic antibody targeting six of the 10 human FZDs. We first identified an anti-FZD antagonist antibody (F2) with a specificity profile matching that of OMP-18R5, a monoclonal antibody that inhibits growth of many cancers by targeting FZD7, FZD1, FZD2, FZD5 and FZD8. Read More

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http://dx.doi.org/10.1080/19420862.2018.1515565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284576PMC
September 2018
19 Reads