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Antibodies
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Higher Order Structure Characterization of Therapeutic Antibodies-Second Volume
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Higher Order Structure Characterization of Therapeutic Antibodies-Second Volume

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

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 8001

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 the 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 aids in the evasion of 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 both traditional and emerging technologies for HOS characterization with an emphasis on studies on the relationship between structure and function, critical quality attribute assessments, immunogenicity, pharmacokinetics, and structural comparability.

Dr. Aaron T. Wecksle
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 (3 papers)

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Research

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8 pages, 1358 KiB  
Communication
Bioprocess Development and Characterization of a 13C-Labeled Hybrid Bispecific Antibody Produced in Escherichia coli
by Aaron T. Wecksler, Victor Lundin, Ambrose J. Williams, Karthik Veeravalli, Dorothea E. Reilly and Sung-Hye Grieco
Antibodies 2023, 12(1), 16; https://doi.org/10.3390/antib12010016 - 14 Feb 2023
Cited by 2 | Viewed by 1800
Abstract
Monoclonal antibodies (mAbs) are highly efficacious therapeutics; however, due to their large, dynamic nature, structural perturbations and regional modifications are often difficult to study. Moreover, the homodimeric, symmetrical nature of mAbs makes it difficult to elucidate which heavy chain (HC)-light chain (LC) pairs [...] Read more.
Monoclonal antibodies (mAbs) are highly efficacious therapeutics; however, due to their large, dynamic nature, structural perturbations and regional modifications are often difficult to study. Moreover, the homodimeric, symmetrical nature of mAbs makes it difficult to elucidate which heavy chain (HC)-light chain (LC) pairs are responsible for any structural changes, stability concerns, and/or site-specific modifications. Isotopic labeling is an attractive means for selectively incorporating atoms with known mass differences to enable identification/monitoring using techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR). However, the isotopic incorporation of atoms into proteins is typically incomplete. Here we present a strategy for incorporating 13C-labeling of half antibodies using an Escherichia coli fermentation system. Unlike previous attempts to generate isotopically labeled mAbs, we provide an industry-relevant, high cell density process that yielded >99% 13C-incorporation using 13C-glucose and 13C-celtone. The isotopic incorporation was performed on a half antibody designed with knob-into-hole technology to enable assembly with its native (naturally abundant) counterpart to generate a hybrid bispecific (BsAb) molecule. This work is intended to provide a framework for producing full-length antibodies, of which half are isotopically labeled, in order to study the individual HC-LC pairs. Full article
(This article belongs to the Special Issue Higher Order Structure Characterization of Therapeutic Antibodies-Second Volume)
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45 pages, 4126 KiB  
Article
IMGT® Nomenclature of Engineered IGHG Variants Involved in Antibody Effector Properties and Formats
by Marie-Paule Lefranc and Gérard Lefranc
Antibodies 2022, 11(4), 65; https://doi.org/10.3390/antib11040065 - 18 Oct 2022
Cited by 3 | Viewed by 2874
Abstract
The constant region of the immunoglobulin (IG) or antibody heavy gamma chain is frequently engineered to modify the effector properties of the therapeutic monoclonal antibodies. These variants are classified in regards to their effects on effector functions, antibody-dependent cytotoxicity (ADCC), antibody-dependent phagocytosis (ADCP), [...] Read more.
The constant region of the immunoglobulin (IG) or antibody heavy gamma chain is frequently engineered to modify the effector properties of the therapeutic monoclonal antibodies. These variants are classified in regards to their effects on effector functions, antibody-dependent cytotoxicity (ADCC), antibody-dependent phagocytosis (ADCP), complement-dependent cytotoxicity (CDC) enhancement or reduction, B cell inhibition by the coengagement of antigen and FcγR on the same cell, on half-life increase, and/or on structure such as prevention of IgG4 half-IG exchange, hexamerisation, knobs-into-holes and the heteropairing H-H of bispecific antibodies, absence of disulfide bridge inter H-L, absence of glycosylation site, and site-specific drug attachment engineered cysteine. The IMGT engineered variant identifier is comprised of the species and gene name (and eventually allele), the letter ‘v’ followed by a number (assigned chronologically), and for each concerned domain (e.g, CH1, h, CH2 and CH3), the novel AA (single letter abbreviation) and IMGT position according to the IMGT unique numbering for the C-domain and between parentheses, the Eu numbering. IMGT engineered variants are described with detailed amino acid changes, visualized in motifs based on the IMGT numbering bridging genes, sequences, and structures for higher order description. Full article
(This article belongs to the Special Issue Higher Order Structure Characterization of Therapeutic Antibodies-Second Volume)
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Review

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16 pages, 2251 KiB  
Review
Structural Investigation of Therapeutic Antibodies Using Hydroxyl Radical Protein Footprinting Methods
by Corie Y. Ralston and Joshua S. Sharp
Antibodies 2022, 11(4), 71; https://doi.org/10.3390/antib11040071 - 14 Nov 2022
Cited by 7 | Viewed by 2470
Abstract
Commercial monoclonal antibodies are growing and important components of modern therapies against a multitude of human diseases. Well-known high-resolution structural methods such as protein crystallography are often used to characterize antibody structures and to determine paratope and/or epitope binding regions in order to [...] Read more.
Commercial monoclonal antibodies are growing and important components of modern therapies against a multitude of human diseases. Well-known high-resolution structural methods such as protein crystallography are often used to characterize antibody structures and to determine paratope and/or epitope binding regions in order to refine antibody design. However, many standard structural techniques require specialized sample preparation that may perturb antibody structure or require high concentrations or other conditions that are far from the conditions conducive to the accurate determination of antigen binding or kinetics. We describe here in this minireview the relatively new method of hydroxyl radical protein footprinting, a solution-state method that can provide structural and kinetic information on antibodies or antibody–antigen interactions useful for therapeutic antibody design. We provide a brief history of hydroxyl radical footprinting, examples of current implementations, and recent advances in throughput and accessibility. Full article
(This article belongs to the Special Issue Higher Order Structure Characterization of Therapeutic Antibodies-Second Volume)
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