1,082 results match your criteria mAbs [Journal]


Effects of terminal galactose residues in mannose α1-6 arm of Fc-glycan on the effector functions of therapeutic monoclonal antibodies.

MAbs 2019 Apr 16. Epub 2019 Apr 16.

a Division of Biological Chemistry and Biologicals , National Institute of Health Sciences , 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa , 210-9501 , Japan.

Typical crystallizable fragment (Fc) glycans attached to the CH2 domain in therapeutic monoclonal antibodies (mAbs) are core-fucosylated and asialo-biantennary complex-type glycans, e.g., G2F (full galactosylation), G1aF (terminal galactosylation on the Man α1-6 arm), G1bF (terminal galactosylation on the Man α1-3 arm), and G0F (non-galactosylation). Read More

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http://dx.doi.org/10.1080/19420862.2019.1608143DOI Listing
April 2019
1 Read

An in vitro FcRn-dependent transcytosis assay as a screening tool for predictive assessment of non-specific clearance of antibody therapeutics in humans.

MAbs 2019 Apr 14. Epub 2019 Apr 14.

a Department of BioAnalytical Sciences.

A cell-based assay employing Madin-Darby canine kidney cells stably expressing human neonatal Fc receptor (FcRn) heavy chain and β2-microglobulin genes was developed to measure transcytosis of monoclonal antibodies (mAbs) under conditions relevant to the FcRn-mediated IgG salvage pathway. The FcRn-dependent transcytosis assay is modeled to reflect combined effects of non-specific interactions between mAbs and cells, cellular uptake via pinocytosis, pH-dependent interactions with FcRn, and dynamics of intracellular trafficking and sorting mechanisms. Evaluation of 53 mAbs, including 30 marketed mAb drugs, revealed a notable correlation between the transcytosis readouts and clearance in humans. Read More

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http://dx.doi.org/10.1080/19420862.2019.1605270DOI Listing
April 2019
4.558 Impact Factor

Neonatal Fc receptor expression in macrophages is indispensable for IgG homeostasis.

MAbs 2019 Apr 9. Epub 2019 Apr 9.

a Department of Molecular and Cellular Medicine , Texas A&M University Health Science Center , 469 Joe H. Reynolds Medical Sciences Building, 1114 TAMU, College Station, Texas 77843 , USA.

The maintenance of the homeostasis of immunoglobulin G (IgG) represents a fundamental aspect of humoral immunity that has direct relevance to the successful delivery of antibody-based therapeutics. The ubiquitously-expressed neonatal Fc receptor (FcRn) salvages IgG from cellular degradation following pinocytic uptake into cells, conferring prolonged in vivo persistence on IgG. However, the cellular sites of FcRn function are poorly defined. Read More

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http://dx.doi.org/10.1080/19420862.2019.1602459DOI Listing

Diabody-Ig: a novel platform for the generation of multivalent and multispecific antibody molecules.

MAbs 2019 Apr 5. Epub 2019 Apr 5.

a Institute of Cell Biology and Immunology , University of Stuttgart , Allmandring 31, 70569 Stuttgart , Germany.

Multivalent mono- or bispecific antibodies are of increasing interest for therapeutic applications, such as efficient receptor clustering and activation, or dual targeting approaches. Here, we present a novel platform for the generation of Ig-like molecules, designated diabody-Ig (Db-Ig). The antigen-binding site of Db-Ig is composed of a diabody in the V-V orientation stabilized by fusion to antibody-derived homo- or heterodimerization domains, e. Read More

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http://dx.doi.org/10.1080/19420862.2019.1603024DOI Listing
April 2019
2 Reads

Important roles of CD32 in promoting suppression of IL-4 induced immune responses by a novel anti-IL-4Rα therapeutic antibody.

MAbs 2019 Apr 5. Epub 2019 Apr 5.

a 3sBio Inc ., 399 Libing road, Zhangjiang, Pudong , Shanghai , 201203 , China.

Asthma is characterized by airway hyper-responsiveness and inflammation, as well as underlying structural changes to the airways. Interleukin-4 (IL-4) is a key T-helper type 2 (Th2) cytokine that plays important roles in the pathogenesis of atopic and eosinophilic asthma. We developed a novel humanized anti-IL-4Rα antibody that can potently inhibit IL-4/IL-13-mediated TF-1 cell proliferation. Read More

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http://dx.doi.org/10.1080/19420862.2019.1601985DOI Listing
April 2019
1 Read

From Rhesus macaque to human: structural evolutionary pathways for immunoglobulin G subclasses.

MAbs 2019 Apr 2:1-16. Epub 2019 Apr 2.

a Division of Vaccine Research , Institute of Human Virology of University of Maryland School of Medicine , Baltimore , MD , USA.

The Old World monkey, Rhesus macaque (Macaca mulatta, Mm), is frequently used as a primate model organism in the study of human disease and to test new vaccines/antibody treatments despite diverging before chimpanzees and orangutans. Mm and humans share 93% genome identity with substantial differences in the genes of the adaptive immune system that lead to different functional IgG subclass characteristics, Fcγ receptors expressed on innate immune cells, and biological interactions. These differences put limitations on Mm use as a primary animal model in the study of human disease and to test new vaccines/antibody treatments. Read More

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http://dx.doi.org/10.1080/19420862.2019.1589852DOI Listing
April 2019
4.558 Impact Factor

Improved monovalent TNF receptor 1-selective inhibitor with novel heterodimerizing Fc.

MAbs 2019 Mar 31:1-13. Epub 2019 Mar 31.

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

The development of alternative therapeutic strategies to tumor necrosis factor (TNF)-blocking antibodies for the treatment of inflammatory diseases has generated increasing interest. In particular, selective inhibition of TNF receptor 1 (TNFR1) promises a more precise intervention, tackling only the pro-inflammatory responses mediated by TNF while leaving regenerative and pro-survival signals transduced by TNFR2 untouched. We recently generated a monovalent anti-TNFR1 antibody fragment (Fab 13. Read More

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http://dx.doi.org/10.1080/19420862.2019.1596512DOI Listing
March 2019
1 Read

Fast protein sequencing of monoclonal antibody by real-time digestion on emitter during nanoelectrospray.

MAbs 2019 Mar 28. Epub 2019 Mar 28.

a Department of Analytical Chemistry , Regeneron Pharmaceuticals, Inc ., Tarrytown , NY 10591.

Growth in the pharmaceutical industry has led to an increasing demand for rapid characterization of therapeutic monoclonal antibodies. The current methods for antibody sequence confirmation (e.g. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2019.1
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http://dx.doi.org/10.1080/19420862.2019.1599633DOI Listing
March 2019
2 Reads

Process optimization and protein engineering mitigated manufacturing challenges of a monoclonal antibody with liquid-liquid phase separation issue by disrupting inter-molecule electrostatic interactions.

MAbs 2019 Mar 27:1-14. Epub 2019 Mar 27.

b Purification Process Sciences , AstraZeneca , Gaithersburg , MD , USA.

We report a case study in which liquid-liquid phase separation (LLPS) negatively impacted the downstream manufacturability of a therapeutic mAb. Process parameter optimization partially mitigated the LLPS, but limitations remained for large-scale manufacturing. Electrostatic interaction driven self-associations and the resulting formation of high-order complexes are established critical properties that led to LLPS. Read More

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http://dx.doi.org/10.1080/19420862.2019.1599634DOI Listing
March 2019
4.558 Impact Factor

The impact of standard accelerated stability conditions on antibody higher order structure as assessed by mass spectrometry.

MAbs 2019 Mar 27:1-12. Epub 2019 Mar 27.

a Division of Pharmaceutical Analysis, Office of Testing and Research, Office of Pharmaceutical Quality , Center for Drug Evaluation and Research, U.S. Food and Drug Administration , St. Louis , USA.

Protein therapeutic higher order structure (HOS) is a quality attribute that can be assessed to help predict shelf life. To model product shelf-life values, possible sample-dependent pathways of degradation that may affect drug efficacy or safety need to be evaluated. As changes in drug thermal stability over time can be correlated with an increased risk of HOS perturbations, the effect of long-term storage on the product should be measured as a function of temperature. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2019.1
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http://dx.doi.org/10.1080/19420862.2019.1599632DOI Listing
March 2019
2 Reads

Development of a high-throughput solubility screening assay for use in antibody discovery.

MAbs 2019 Mar 26:1-10. Epub 2019 Mar 26.

a BioTechnology Discovery Research , Eli Lilly Biotechnology Center , San Diego , CA , USA.

Poor solubility is a common challenge encountered during the development of high concentration monoclonal antibody (mAb) formulations, but there are currently no methods that can provide predictive information on high-concentration behavior of mAbs in early discovery. We explored the utility of methodologies used for determining extrapolated solubility as a way to rank-order mAbs based on their relative solubility properties. We devised two approaches to accomplish this: 1) vapor diffusion technique utilized in traditional protein crystallization practice, and 2) polyethylene glycol (PEG)-induced precipitation and quantitation by turbidity. Read More

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http://dx.doi.org/10.1080/19420862.2019.1589851DOI Listing

An anti-apoptotic HEK293 cell line provides a robust and high titer platform for transient protein expression in bioreactors.

MAbs 2019 Mar 23:1-10. Epub 2019 Mar 23.

a Department of Cell Culture , Genentech Inc ., South San Francisco , CA , USA.

HEK293 transient expression systems are used to quickly generate proteins for research and pre-clinical studies. With the aim of engineering a high-producing host that grows and transfects robustly in bioreactors, we deleted the pro-apoptotic genes Bax and Bak in an HEK293 cell line. The HEK293 Bax Bak double knock-out (HEK293 DKO) cell line exhibited resistance to apoptosis and shear stress. Read More

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http://dx.doi.org/10.1080/19420862.2019.1598230DOI Listing

Immune repertoire mining for rapid affinity optimization of mouse monoclonal antibodies.

MAbs 2019 Mar 22:1-12. Epub 2019 Mar 22.

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

Traditional hybridoma and B cell cloning antibody discovery platforms have inherent limits in immune repertoire sampling depth. One consequence is that monoclonal antibody (mAb) leads often lack the necessary affinity for therapeutic applications, thus requiring labor-intensive and time-consuming affinity in vitro engineering optimization steps. Here, we show that high-affinity variants of mouse-derived mAbs can be rapidly obtained by testing of somatic sequence variants obtained by deep sequencing of antibody variable regions in immune repertories from immunized mice, even with a relatively sparse sampling of sequence variants from large sequence datasets. Read More

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http://dx.doi.org/10.1080/19420862.2019.1584517DOI Listing

Functional mimetic of the G-protein coupled receptor CXCR4 on a soluble antibody scaffold.

MAbs 2019 Mar 22:1-10. Epub 2019 Mar 22.

a Department of Antibody Discovery and Protein Engineering , AstraZeneca , Gaithersburg , MD , USA.

G-protein coupled receptors (GPCRs) constitute major drug targets due to their involvement in critical biological functions and pathophysiological disorders. The leading challenge in their structural and functional characterization has been the need for a lipid environment to accommodate their hydrophobic cores. Here, we report an antibody scaffold mimetic (ASM) platform where we have recapitulated the extracellular functional domains of the GPCR, C-X-C chemokine receptor 4 (CXCR4) on a soluble antibody framework. Read More

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http://dx.doi.org/10.1080/19420862.2019.1596703DOI Listing
March 2019
3 Reads

Antibody repertoire analysis of mouse immunization protocols using microfluidics and molecular genomics.

MAbs 2019 Mar 21:1-14. Epub 2019 Mar 21.

a GigaGen Inc ., South San Francisco , CA , USA.

Immunization of mice followed by hybridoma or B-cell screening is one of the most common antibody discovery methods used to generate therapeutic monoclonal antibody (mAb) candidates. There are a multitude of different immunization protocols that can generate an immune response in animals. However, an extensive analysis of the antibody repertoires that these alternative immunization protocols can generate has not been performed. Read More

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http://dx.doi.org/10.1080/19420862.2019.1583995DOI Listing

Controlled conductivity at low pH in Protein L chromatography enables separation of bispecific and other antibody formats by their binding valency.

MAbs 2019 Mar 21:1-7. Epub 2019 Mar 21.

d Research Division , Chugai Pharmaceutical Co., Ltd. , Kamakura , Kanagawa , Japan.

The complex molecular formats of recent therapeutic antibodies, including bispecific antibodies, antibody fragments, and other fusion proteins, makes the task of purifying the desired molecules in a limited number of purification steps more and more challenging. Manufacturing these complicated biologics can be substantially improved in the affinity capture stage if the simple bind-and-elute mode is accompanied by targeted removal of the impurities, such as mis-paired antibodies and oligomers or aggregates. Here, we report a method, based on the binding valency to Protein L resin, of separating proteins during the elution step by simply controlling the conductivity at low pH. Read More

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http://dx.doi.org/10.1080/19420862.2019.1583996DOI Listing
March 2019
1 Read

Detection and quantification of free sulfhydryls in monoclonal antibodies using maleimide labeling and mass spectrometry.

MAbs 2019 Mar 20:1-10. Epub 2019 Mar 20.

a Human Health Therapeutics Research Centre , National Research Council of Canada , Ottawa , Ontario , Canada.

The detection of free sulfhydryls in proteins can reveal incomplete disulfide bond formation, indicate cysteine residues available for conjugation, and offer insights into protein stability and structure. Traditional spectroscopic methods of free sulfhydryl detection, such as Ellman's reagent, generally require a relatively large amount of sample, preventing their use for the analysis of biotherapeutics early in the development cycle. These spectroscopic methods also cannot accurately determine the location of the free sulfhydryl, further limiting their utility. Read More

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http://dx.doi.org/10.1080/19420862.2019.1595307DOI Listing

Combining the best of two worlds: highly flexible chimeric antigen receptor adaptor molecules (CAR-adaptors) for the recruitment of chimeric antigen receptor T cells.

MAbs 2019 Mar 20:1-11. Epub 2019 Mar 20.

a Roche Pharmaceutical Research & Early Development , Roche Innovation Center Zurich , Schlieren , Switzerland.

Chimeric antigen receptor (CAR)-engineered T cells have a proven efficacy for the treatment of refractory hematological B cell malignancies. While often accompanied by side effects, CAR-T technology is getting more mature and will become an important treatment option for various tumor indications. In this review, we summarize emerging approaches that aim to further evolve CAR-T cell therapy based on combinations of so-called universal or modular CAR-(modCAR-)T cells, and their respective adaptor molecules (CAR-adaptors), which mediate the crosslinking between target and effector cells. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2019.1
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http://dx.doi.org/10.1080/19420862.2019.1596511DOI Listing
March 2019
11 Reads

Glycosylation-independent binding of monoclonal antibody toripalimab to FG loop of PD-1 for tumor immune checkpoint therapy.

MAbs 2019 Mar 20:1-10. Epub 2019 Mar 20.

b Institute of Physical Science and Information Technology , Anhui University , Hefei , China.

Monoclonal antibody (mAb)-based blockade of programmed cell death 1 (PD-1) or its ligand to enable antitumor T-cell immunity has been successful in treating multiple tumors. However, the structural basis of the binding mechanisms of the mAbs and PD-1 and the effects of glycosylation of PD-1 on mAb interaction are not well understood. Here, we report the complex structure of PD-1 with toripalimab, a mAb that is approved by China National Medical Products Administration as a second-line treatment for melanoma and is under multiple Phase 1-Phase 3 clinical trials in both China and the US. Read More

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http://dx.doi.org/10.1080/19420862.2019.1596513DOI Listing
March 2019
3 Reads

Hydrogen/deuterium exchange-mass spectrometry analysis of high concentration biotherapeutics: application to phase-separated antibody formulations.

MAbs 2019 Mar 19:1-10. Epub 2019 Mar 19.

a Bioproduct Research and Development , Lilly Research Laboratories, Eli Lilly and Company , Indianapolis , IN , USA.

High concentration biotherapeutic formulations are often required to deliver large doses of drugs to achieve a desired degree of efficacy and less frequent dose. However, highly concentrated protein-containing solutions may exhibit undesirable therapeutic properties, such as increased viscosity, aggregation, and phase separation that can affect drug efficacy and raise safety issues. The characterization of high concentration protein formulations is a critical yet challenging analytical task for therapeutic development efforts, due to the lack of technologies capable of making accurate measurements under such conditions. Read More

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http://dx.doi.org/10.1080/19420862.2019.1589850DOI Listing
March 2019
2 Reads

Design and characterization of homogenous antibody-drug conjugates with a drug-to-antibody ratio of one prepared using an engineered antibody and a dual-maleimide pyrrolobenzodiazepine dimer.

MAbs 2019 04 5;11(3):500-515. Epub 2019 Mar 5.

a Antibody Discovery and Protein Engineering , MedImmune , Gaithersburg , MD , USA.

Most strategies used to prepare homogeneous site-specific antibody-drug conjugates (ADCs) result in ADCs with a drug-to-antibody ratio (DAR) of two. Here, we report a disulfide re-bridging strategy to prepare homogeneous ADCs with DAR of one using a dual-maleimide pyrrolobenzodiazepine (PBD) dimer (SG3710) and an engineered antibody (Flexmab), which has only one intrachain disulfide bridge at the hinge. We demonstrate that SG3710 efficiently re-bridge a Flexmab targeting human epidermal growth factor receptor 2 (HER2), and the resulting ADC was highly resistant to payload loss in serum and exhibited potent anti-tumor activity in a HER2-positive gastric carcinoma xenograft model. Read More

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http://dx.doi.org/10.1080/19420862.2019.1578611DOI Listing
April 2019
1 Read

Impact of N-glycosylation on Fcγ receptor / IgG interactions: unravelling differences with an enhanced surface plasmon resonance biosensor assay based on coiled-coil interactions.

MAbs 2019 04 5;11(3):435-452. Epub 2019 Mar 5.

a Department of Chemical Engineering , Polytechnique Montréal , Montréal , Québec , Canada.

The N-glycosylation profile of immunoglobulin G (IgG) is considered a critical quality attribute due to its impact on IgG-Fc gamma receptor (FcγR) interactions, which subsequently affect antibody-dependent cell-based immune responses. In this study, we investigated the impact of the FcγR capture method, as well as FcγR N-glycosylation, on the kinetics of interaction with various glycoforms of trastuzumab (TZM) in a surface plasmon resonance (SPR) biosensor assay. More specifically, we developed a novel strategy based on coiled-coil interactions for the stable and oriented capture of coil-tagged FcγRs at the biosensor surface. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2019.1
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http://dx.doi.org/10.1080/19420862.2019.1581017DOI Listing
April 2019
3 Reads

Integrin α-3 ß-1's central role in breast cancer, melanoma and glioblastoma cell aggregation revealed by antibodies with blocking activity.

MAbs 2019 Apr 16:1-18. Epub 2019 Apr 16.

a The Developmental Studies Hybridoma Bank, Department of Biology , University of Iowa , Iowa City , IA , USA.

Breast cancer, melanoma and glioblastoma cells undergo cell-mediated aggregation and aggregate coalescence in a transparent 3D Matrigel environment. Cells from normal tissue and non-tumorigenic cell lines do not exhibit these behaviors. Here, 266 monoclonal antibodies (mAbs) demonstrated to interact with a wide variety of membrane, secreted and matrix proteins, have been screened for their capacity to block these tumorigenic cell-specific behaviors in a 3D environment. Read More

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http://dx.doi.org/10.1080/19420862.2019.1583987DOI Listing
April 2019
1 Read

Physicochemical and functional assessments demonstrating analytical similarity between rituximab biosimilar HLX01 and the MabThera®.

MAbs 2019 04 22;11(3):606-620. Epub 2019 Feb 22.

a Shanghai Henlius Biotech, Inc ., Shanghai , China.

Development of bio-therapeutics has exhibited exponential growth in China over the past decade. However, no biosimilar drug has been approved in China (CN) due to the lack of a national biosimilar regulatory guidance. HLX01, a rituximab biosimilar developed in China under European Medicines Agency biosimilar guidelines and requirements, was the first such drug submitted for regulatory review in China, and it is expected to receive approval there as a biosimilar product. Read More

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http://dx.doi.org/10.1080/19420862.2019.1578147DOI Listing
April 2019
1 Read

Structural characterization of monoclonal antibodies targeting C-terminal Ser region of phosphorylated tau protein.

MAbs 2019 04 26;11(3):477-488. Epub 2019 Feb 26.

a Department of Biochemistry & Molecular Pharmacology , New York University School of Medicine , New York , NY , USA.

Targeting tau with immunotherapies is currently the most common approach taken in clinical trials of patients with Alzheimer's disease. The most prominent pathological feature of tau is its hyperphosphorylation, which may cause the protein to aggregate into toxic assemblies that collectively lead to neurodegeneration. Of the phospho-epitopes, the region around Ser/Ser has received particular attention for therapeutic targeting because of its prominence and stability in diseased tissue. Read More

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http://dx.doi.org/10.1080/19420862.2019.1574530DOI Listing
April 2019
1 Read

Capture and display of antibodies secreted by hybridoma cells enables fluorescent on-cell screening.

MAbs 2019 04 22;11(3):546-558. Epub 2019 Feb 22.

a Lankenau Institute for Medical Research , Wynnewood , PA , USA.

Hybridoma methods for monoclonal antibody (mAb) cloning are a mainstay of biomedical research, but they are hindered by the need to maintain hybridomas in oligoclonal pools during antibody screening. Here, we describe a system in which hybridomas specifically capture and display the mAbs they secrete: On-Cell mAb Screening (OCMS™). In OCMS™, mAbs displayed on the cell surface can be rapidly assayed for expression level and binding specificity using fluorescent antigens with high-content (image-based) methods or flow cytometry. Read More

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http://dx.doi.org/10.1080/19420862.2019.1574520DOI Listing
April 2019
2 Reads

Charge variants characterization and release assay development for co-formulated antibodies as a combination therapy.

MAbs 2019 04 20;11(3):489-499. Epub 2019 Feb 20.

a Department of Analytical Sciences , MedImmune , Gaithersburg , MD , USA.

Combination therapy is a fast-growing strategy to maximize therapeutic benefits to patients. Co-formulation of two or more therapeutic proteins has advantages over the administration of multiple medications, including reduced medication errors and convenience for patients. Characterization of co-formulated biologics can be challenging due to the high degree of similarity in the physicochemical properties of co-formulated proteins, especially at different concentrations of individual components. Read More

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https://www.tandfonline.com/doi/full/10.1080/19420862.2019.1
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http://dx.doi.org/10.1080/19420862.2019.1578137DOI Listing
April 2019
2 Reads

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

MAbs 2019 04 12;11(3):532-545. Epub 2019 Feb 12.

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
April 2019
1 Read

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380415PMC
February 2019

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

MAbs 2019 Feb 20:1-14. Epub 2019 Feb 20.

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
February 2019
6 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 04 26;11(3):559-568. Epub 2019 Feb 26.

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

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
April 2019
2 Reads

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

MAbs 2019 04 22;11(3):569-582. 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
April 2019
1 Read

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

MAbs 2019 04 26;11(3):516-531. Epub 2019 Feb 26.

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

We describe here the design, construction and validation of ALTHEA Gold Libraries™. These single-chain variable fragment (scFv), 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
April 2019
2 Reads

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

MAbs 2019 04 6;11(3):463-476. Epub 2019 Feb 6.

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
April 2019
1 Read

A general platform for antibody purification utilizing engineered-micelles.

MAbs 2019 04 6;11(3):583-592. Epub 2019 Feb 6.

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
April 2019
6 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 04 18;11(3):593-605. Epub 2019 Feb 18.

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
April 2019
7 Reads

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

MAbs 2019 01 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
2 Reads

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

MAbs 2019 01 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
9 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380423PMC
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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380431PMC
December 2018
4 Reads

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380433PMC
December 2018
3 Reads

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380400PMC
December 2018
15 Reads

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

MAbs 2019 01 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
26 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380425PMC
January 2019
1 Read

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380435PMC
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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380392PMC
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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380391PMC
January 2019
4.558 Impact Factor

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

MAbs 2019 01 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 01 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
Publisher Site
http://dx.doi.org/10.1080/19420862.2018.1556465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380461PMC
December 2018
33 Reads