Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.6
4.7
Journals
Antibodies
Special Issues
Higher Order Structure Characterization of Therapeutic Antibodies
share announcement

Higher Order Structure Characterization of Therapeutic Antibodies

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

Deadline for manuscript submissions: closed (1 December 2019) | Viewed by 17070

Special Issue Editor

Dr. Aaron T. Wecksler

E-Mail Website
Guest Editor
Department of Protein Analytical Chemistry, Genentech, Inc., Member of the Roche Group 1 DNA Way, South San Francisco, CA 94080, USA
Interests: biotherapeutic structure/function relationship characterization
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue of Antibodies focuses on techniques for structural characterization of biotherapeutic antibodies. The unique structure of therapeutic monoclonal antibodies (mAbs) enables highly specific target recognition, affords the potential for multiple modes of mechanisms of actions (MoAs), and provides evasion for foreign recognition by the immune system. The higher order structure (HOS) of mAbs is an inherent critical quality attribute (CQA), and perturbations in the HOS can lead to immunogenicity and/or loss of efficacy.  Thus, techniques that enable direct and indirect structural characterization are integral for the development and product quality consistency of mAbs. This Special Issue aims to highlight traditional and emerging technologies for HOS characterization with an emphasis on structure/function relationship studies, critical quality attribute assessment, immunogenicity, pharmacokinetics, and structural comparability.

Dr. Aaron T. Wecksler
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibodies is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • therapeutic monoclonal antibodies
  • higher order structure
  • structure/function relationship
  • structural comparability

Published Papers (2 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

19 pages, 3125 KiB  
Article
The Impact of Immunoglobulin G1 Fc Sialylation on Backbone Amide H/D Exchange
by Felix Kuhne, Lea Bonnington, Sebastian Malik, Marco Thomann, Cecile Avenal, Florian Cymer, Harald Wegele, Dietmar Reusch, Michael Mormann and Patrick Bulau
Antibodies 2019, 8(4), 49; https://doi.org/10.3390/antib8040049 - 1 Oct 2019
Cited by 15 | Viewed by 6522
Abstract
The usefulness of higher-order structural information provided by hydrogen/deuterium exchange-mass spectrometry (H/DX-MS) for the structural impact analyses of chemical and post-translational antibody modifications has been demonstrated in various studies. However, the structure–function assessment for protein drugs in biopharmaceutical research and development is often [...] Read more.
The usefulness of higher-order structural information provided by hydrogen/deuterium exchange-mass spectrometry (H/DX-MS) for the structural impact analyses of chemical and post-translational antibody modifications has been demonstrated in various studies. However, the structure–function assessment for protein drugs in biopharmaceutical research and development is often impeded by the relatively low-abundance (below 5%) of critical quality attributes or by overlapping effects of modifications, such as glycosylation, with chemical amino acid modifications; e.g., oxidation or deamidation. We present results demonstrating the applicability of the H/DX-MS technique to monitor conformational changes of specific Fc glycosylation variants produced by in vitro glyco-engineering technology. A trend towards less H/DX in Fc Cγ2 domain segments correlating with larger glycan structures could be confirmed. Furthermore, significant deuterium uptake differences and corresponding binding properties to Fc receptors (as monitored by SPR) between α-2,3- and α-2,6-sialylated Fc glycosylation variants were verified at sensitive levels. Full article
(This article belongs to the Special Issue Higher Order Structure Characterization of Therapeutic Antibodies)
►▼ Show Figures

Figure 1

19 pages, 3153 KiB  
Article
Distinguishing Between Monomeric scFv and Diabody in Solution Using Light and Small Angle X-ray Scattering
by Frank Lüdel, Sandra Bufe, Willem M. Bleymüller, Hugo de Jonge, Luisa Iamele, Hartmut H. Niemann and Thomas Hellweg
Antibodies 2019, 8(4), 48; https://doi.org/10.3390/antib8040048 - 23 Sep 2019
Cited by 6 | Viewed by 10006
Abstract
Depending on the linker length between the V H and the V L domain, single-chain Fv (scFv) antibody fragments form monomers, dimers (diabodies) or higher oligomers. We aimed at generating a diabody of the anti-MET antibody 3H3 to use it as crystallization chaperone [...] Read more.
Depending on the linker length between the V H and the V L domain, single-chain Fv (scFv) antibody fragments form monomers, dimers (diabodies) or higher oligomers. We aimed at generating a diabody of the anti-MET antibody 3H3 to use it as crystallization chaperone to promote crystallization of the MET ectodomain through the introduction of a pre-formed twofold axis of symmetry. Size exclusion chromatography, however, suggested the protein to be monomeric. Hence, we used scattering techniques applied to solutions to further investigate its oligomerization state. The small angle X-ray scattering (SAXS) curve measured for our protein nicely fits to the scattering curve calculated from the known crystal structure of a diabody. In addition, concentration-dependent photon correlation spectroscopy (PCS) measurements revealed a hydrodynamic radius of 3.4 nm at infinite dilution and a negative interaction parameter k D , indicating attractive interactions that are beneficial for crystallization. Both SAXS and PCS measurements clearly suggest our antibody fragment to be a diabody in solution. Chemical cross-linking with glutaraldehyde and cell motility assays confirmed this conclusion. Full article
(This article belongs to the Special Issue Higher Order Structure Characterization of Therapeutic Antibodies)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-2
Back to TopTop