The Antibody Society

the official website of the antibody society

The Antibody Society

An international non-profit supporting antibody-related research and development.

The Antibody Society at Antibody Engineering & Therapeutics 2018

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The Antibody Society held its 2018 annual meeting at Antibody Engineering & Therapeutics in San Diego on December 9-13. It was a a great opportunity for the board members and volunteers to meet our society members and provide updates on Society initiatives.

Informative keynote addresses were given by Prof. Andreas Plückthun (University of Zurich), Prof. David Baker (University of Washington), Prof. Rachael Clark (Harvard Medical School) and Dr. Badrul Chowdhury (Medimmune).

One of the highlights of the conference was the Antibodies to Watch in 2019 presentation by Dr. Janice Reichert (Executive Director of TAbS and Editor-in-Chief of mAbs).

The Antibody Society booth at Antibody Engineering &Therapeutics

Most read from mAbs

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The Antibody Society is pleased and proud to be affiliated with mAbs, a multi-disciplinary journal dedicated to advancing the art and science of antibody research and development. We hope you enjoy these summaries based on the abstracts of the most read papers published in a recent issue. All the articles are open access; PDFs can be downloaded by following the links below.

Issue 10.8 (November/December 2018)

Rapid, automated characterization of disulfide bond scrambling and IgG2 isoform determination. In this new report, Resemann et al. discuss a rapid LC-MALDI-TOF/TOF workflow that can both identify the IgG2 disulfide linkages and provide a semi-quantitative assessment of the distribution of the disulfide isoforms. They established signature disulfide-bonded IgG2 hinge peptides that correspond to the A, A/B, and B disulfide isoforms, and can be applied to the fast classification of IgG2 isoforms in heterogeneous mixtures.

Charge variant native mass spectrometry benefits mass precision and dynamic range of monoclonal antibody intact mass analysis. Bailey et al. describe charge variant native mass spectrometry (CVMS), an integrated native ion exchange mass spectrometry-based charge variant analytical approach that delivers detailed molecular information in a single, semi-automated analysis. They used pure volatile salt mobile phases over a pH gradient that effectively separated variants based on minimal differences in isoelectric point. Characterization of variants such as deamidation, which are traditionally unattainable by intact mass due to their minimal molecular weight differences, were measured unambiguously by mass and retention time to allow confident MS1 identification. The authors demonstrated that efficient chromatographic separation allows introduction of the purified forms of the charge variant isoforms into the Orbitrap mass spectrometer. Based on their results, they conclude that the CVMS method allows confident assignment of intact monoclonal antibody isoforms of similar mass and relative abundance measurements across three orders of magnitude dynamic range.

A systematic approach for analysis and characterization of mispairing in bispecific antibodies with asymmetric architecture. In this new report, Wang et al. discuss a systematic approach for analysis and characterization of mispairing in asymmetric bispecific antibodies. This approach consists of three orthogonal components, the first of which is a liquid chromatography (LC)-mass spectrometry (MS)–based method to measure the mass of intact antibodies. This method is used for fast analysis of mispairing and requires minimal method development, which makes it an ideal choice for early-stage development. The second component is a hydrophobic interaction chromatography (HIC)–based mispairing method that is suitable for lot release testing. The HIC method is robust and quality control friendly, and offers great linearity, precision, and accuracy. The third component is a two-dimensional LC-MS method for on-line chromatographic peak identification, which not only expedites this task but also reduces the risk of undesirable modifications during conventional fraction collection. These three methods dovetail to form the foundation of a complementary toolbox for analysis and characterization of mispairing in asymmetric bispecific antibodies and provide guidance and support for process development throughout the drug development life cycle.

Characterization and analysis of scFv-IgG bispecific antibody size variants. Cao et al. report size variants that were observed for an appended scFv-IgG bispecific antibody. Structural characterization studies showed that the size variants resulted from the engineered disulfide bond on the scFv, whereby the engineered disulfide was found to be either open or unable to form an intrachain disulfide bond due to cysteinylation or glutathionylation of the cysteines. Furthermore, the scFv engineered cysteines also formed intermolecular disulfide bonds, leading to the formation of highly stable dimers and aggregates. Because both the monomer variants and dimers showed lower bioactivity, they were considered to be product-related impurities that must be monitored and controlled. To this end, the authors developed and optimized a robust, precise, and accurate high-resolution size-exclusion chromatographic method, using a statistical design-of-experiments methodology.

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First approval for emapalumab

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On November 20, 2018, the US Food and Drug Administration approved emapalumab (Gamifant) for the treatment of pediatric (newborn and above) and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) who have refractory, recurrent or progressive disease or intolerance with conventional HLH therapy. Developed by NovImmune SA, emapalumab is a human IgG1 antibody that targets interferon gamma. Emapalumab has received a variety of designations intended to facilitate the development of drugs for rare, serious or life-threatening diseases, including Breakthrough Therapy, Rare Pediatric Disease, and Orphan Drug designations in the US, and Priority Medicines and Orphan Drug designations in the EU. The FDA’s approval was based in part on a clinical study of 27 pediatric patients with suspected or confirmed primary HLH with either refractory, recurrent or progressive disease during conventional HLH therapy or who were intolerant of conventional HLH therapy. Results from this study showed that 63% of patients experienced a response and 70% were able to proceed to stem cell transplant. A marketing application for emapalumab is undergoing evaluation by the European Medicines Agency.

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Winners of the Antibody Engineering & Therapeutics Student/Postdoc Poster Competition

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Congratulations to our winners!

To recognize the research activities of promising student and postdoctoral attendees of Antibody Engineering & Therapeutics, The Antibody Society sponsors a competition for our student/postdoc members who submit posters for display at the meeting. Our judges select the best work based on originality, relevance and perceived impact on the field of antibody R&D.

This year, our judges selected 3 student/postdocs winners who receive: 1) a complimentary registration to attend the conference and pre-conference sessions; 2) an opportunity to give a short oral presentation of their work in one of the conference sessions; and 3) support for travel expenses.

The winners of the contest are:

Madeleine Jennewein (Ph.D. candidate, Harvard University). Poster title: Trans-placental antibody transfer selects for highly functional antibodies

Junpeng Qi (Postdoctoral Associate, The Scripps Research Institute. Poster title: Potent and selective antitumor activity of a T cell-engaging bispecific antibody targeting a membrane-proximal epitope of ROR1

Pietro Sormanni (Borysiewicz Biomedical Sciences Fellow (postdoctoral), University of Cambridge). Poster title: Third generation antibody discovery: In silico rational design

Antibody Engineering & Therapeutics, the annual meeting of The Antibody Society, is managed by KNect365. The meeting will be held December 10-13, 2018 in San Diego, CA. Society members receive a 15% discount on the registration fee. Contact us at membership@antibodysociety.org for the code.

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Congratulations to George P. Smith, Nobel Laureate, Chemistry 2018, for the Invention of Phage Display

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The Antibody Society congratulates Prof. George P. Smith, who will receive a 2018 Nobel Prize in Chemistry this December for his invention of phage display, and pioneering work on phage-library technology.

Read the 3 papers that started the field:

-Invention of phage display (Smith GP. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science 1985)

– Improving phage display and affinity selection (Parmley SF, Smith GP. Antibody-selectable filamentous fd phage vectors: affinity purification of target genes. Gene 1988)

– Proof of concept for phage-displayed peptide libraries (Scott JK, Smith GP. Searching for peptide ligands with an epitope library. Science 1990)

As a postdoc with Prof. Smith, The Antibody Society Board Member Dr. Jamie K. Scott helped produce the proof of concept for phage-displayed peptide libraries.