Analytical Methodologies for Antibodies

A special issue of Antibodies (ISSN 2073-4468).

Deadline for manuscript submissions: closed (30 March 2018) | Viewed by 56225

Special Issue Editors


E-Mail Website
Guest Editor
BioAnalytical Sciences, Eli Lilly and Company, 22 Imclone Drive, Branchburg, NJ 08619, USA
Interests: bioanalytical characterization; antibody development; monoclonal antibodies

E-Mail Website
Guest Editor
BioAnalytical Sciences, Eli Lilly and Company, 22 Imclone Drive, Branchburg, NJ 08619, USA
Interests: bioanalytical characterization; antibody development; monoclonal antibodies

Special Issue Information

Dear Colleagues,

The ever advancing knowledge of antibody production, specificity, function, and utility has allowed for an evolution in the impact that these proteins have, ranging from uses as critical assay reagents through treatment of various diseases by way of novel therapeutic biomedicines. This diverse array of applications for both polyclonal and monoclonal antibodies requires an analytical toolbox by which to fully characterize these proteins in order to fully understand their molecular properties and implicit function. Analytical techniques continually evolve and have become applicable to probe the chemical composition, structural dynamics, and physical mechanisms which define these highly specialized proteins.

This Special Issue of Antibodies focuses on the analytical methodologies used for the biomolecular understanding of antibody molecules. Emphasizing newly developing and novel analytical approaches, this issue highlights biological, biochemical, and biophysical characterization strategies for the comprehensive understanding of the attributes that define such invaluable protein species.

Dr. Ming-Ching Hsieh
Dr. Matthew T. Mazur
Guest Editors

Manuscript Submission Information

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Keywords

  • Antibody development

  • Bioanalytical characterization

  • Antibody/antigen interaction

  • Structural elucidation

  • Structure and function relationship

  • Bioanalytical method development

  • Effector functionalities

  • Method qualification and validation

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Published Papers (3 papers)

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Research

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19 pages, 5588 KiB  
Article
Evaluation of Continuous Membrane Chromatography Concepts with an Enhanced Process Simulation Approach
by Steffen Zobel-Roos, Dominik Stein and Jochen Strube
Antibodies 2018, 7(1), 13; https://doi.org/10.3390/antib7010013 - 2 Mar 2018
Cited by 23 | Viewed by 8453
Abstract
Modern biopharmaceutical products strive for small-scale, low-cost production. Continuous chromatography has shown to be a promising technology because it assures high-capacity utilization, purity and yield increases, and lower facility footprint. Membrane chromatography is a fully disposable low-cost alternative to bead-based chromatography with minor [...] Read more.
Modern biopharmaceutical products strive for small-scale, low-cost production. Continuous chromatography has shown to be a promising technology because it assures high-capacity utilization, purity and yield increases, and lower facility footprint. Membrane chromatography is a fully disposable low-cost alternative to bead-based chromatography with minor drawbacks in terms of capacity. Hence, continuous membrane chromatography should have a high potential. The evaluation of continuous processes goes often along with process modeling. Only few experiments with small feed demand need to be conducted to estimate the model parameters. Afterwards, a variety of different process setups and working points can be analyzed in a very short time, making the approach very efficient. Since the available modeling approaches for membrane chromatography modules did not fit the used design, a new modeling approach is shown. This combines the general rate model with an advanced fluid dynamic distribution. Model parameter determination and model validation were done with industrial cell cultures containing Immunoglobulin G (IgG). The validated model was used to evaluate the feasibility of the integrated Counter Current Chromatography (iCCC) concept and the sequential chromatography concept for membrane adsorber modules, starting with a laboratory-type module used for sample preparation. A case study representing a fed-batch reactor with a capacity from 20 to 2000 L was performed. Compared to batch runs, a 71% higher capacity, 48.5% higher productivity, and 38% lower eluent consumption could be achieved. Full article
(This article belongs to the Special Issue Analytical Methodologies for Antibodies)
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Review

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18 pages, 1451 KiB  
Review
Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity
by Kathleen P. Pratt
Antibodies 2018, 7(2), 19; https://doi.org/10.3390/antib7020019 - 31 May 2018
Cited by 63 | Viewed by 16680
Abstract
The development of anti-drug antibodies (ADAs) following administration of biotherapeutics to patients is a vexing problem that is attracting increasing attention from pharmaceutical and biotechnology companies. This serious clinical problem is also spawning creative research into novel approaches to predict, avoid, and in [...] Read more.
The development of anti-drug antibodies (ADAs) following administration of biotherapeutics to patients is a vexing problem that is attracting increasing attention from pharmaceutical and biotechnology companies. This serious clinical problem is also spawning creative research into novel approaches to predict, avoid, and in some cases even reverse such deleterious immune responses. CD4+ T cells are essential players in the development of most ADAs, while memory B-cell and long-lived plasma cells amplify and maintain these responses. This review summarizes methods to predict and experimentally identify T-cell and B-cell epitopes in therapeutic proteins, with a particular focus on blood coagulation factor VIII (FVIII), whose immunogenicity is clinically significant and is the subject of intensive current research. Methods to phenotype ADA responses in humans are described, including T-cell stimulation assays, and both established and novel approaches to determine the titers, epitopes and isotypes of the ADAs themselves. Although rational protein engineering can reduce the immunogenicity of many biotherapeutics, complementary, novel approaches to induce specific tolerance, especially during initial exposures, are expected to play significant roles in future efforts to reduce or reverse these unwanted immune responses. Full article
(This article belongs to the Special Issue Analytical Methodologies for Antibodies)
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20 pages, 6155 KiB  
Review
IgG Antibody 3D Structures and Dynamics
by Jacob White Jay, Brinkley Bray, Yaozhi Qi, Eseosaserea Igbinigie, Hao Wu, Jinping Li and Gang Ren
Antibodies 2018, 7(2), 18; https://doi.org/10.3390/antib7020018 - 19 Apr 2018
Cited by 38 | Viewed by 30486
Abstract
Antibodies are vital for human health because of their ability to function as nature’s drugs by protecting the body from infection. In recent decades, antibodies have been used as pharmaceutics for targeted therapy in patients with cancer, autoimmune diseases, and cardiovascular diseases. Capturing [...] Read more.
Antibodies are vital for human health because of their ability to function as nature’s drugs by protecting the body from infection. In recent decades, antibodies have been used as pharmaceutics for targeted therapy in patients with cancer, autoimmune diseases, and cardiovascular diseases. Capturing the dynamic structure of antibodies and characterizing antibody fluctuation is critical for gaining a deeper understanding of their structural characteristics and for improving drug development. Current techniques for studying three-dimensional (3D) structural heterogeneity and variability of proteins have limitations in ascertaining the dynamic structural behavior of antibodies and antibody-antigen complexes. Here, we review current techniques used to study antibody structures with a focus on the recently developed individual-particle electron tomography (IPET) technique. IPET, as a particle-by-particle methodology for 3D structural characterization, has shown advantages in studying structural variety and conformational changes of antibodies, providing direct imaging data for biomolecular engineering to improve development and clinical application of synthetic antibodies. Full article
(This article belongs to the Special Issue Analytical Methodologies for Antibodies)
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