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You are here: Home / Archives for Antibody discovery

Call for Papers on Biopharmaceutical Informatics

January 19, 2021 by Janice Reichert

As evident from papers published in mAbs in recent years, computation is being increasingly used in the discovery and development of antibody-based biologic drugs. To celebrate the rise of biopharmaceutical informatics directed towards antibody R & D, we invite The Antibody Society members, mAbs readers and the broader scientific community to contribute review articles focused on highlighting how computation has enabled their investigations or led them to new ones. The reviews should narrate the state of the art and speculate on new vistas for computational applications in the field.

We are particularly interested in reviews in the following topics:

  • Analyses of immune repertoires and their role in target validation and drug discovery.
  • Analyses of antibody structure-function relationships with emphasis on therapeutic antibody-based biologics.
  • Structure-based design of antibody fragments (e.g., nanobodies) and antibody-based multi-specific molecular formats.
  • Design of antibody libraries for different display strategies and/or with improved developability.
  • Structure-based affinity maturation and optimization of biologic lead candidates.
  • Molecular simulations of antibodies to understand their solution behaviors, such as aggregation, viscosity and physicochemical degradation.
  • Consideration of developability in biologic drug discovery and design.
  • Developability assessments at early-stage development.
  • Specific and non-specific interactions formed by antibodies in vitro and in vivo.
  • Computation in antibody formulations – design of novel excipients.
  • Applications of artificial Intelligence and machine learning towards antibody discovery, development and manufacturing.
  • Progress and challenges in modeling antibodies and multi-specific formats.
  • Predicting chemical degradation in antibody-based biologic drugs.
  • Optimizing antigens for greater immunization success.

Although these topics are especially of interest, we welcome well-written reviews in related areas as well.

Publication charges will be waived for six of the best review articles selected from pre-submission inquiries, which should consist of the title, abstract and general outline of the intended review article.

The deadline for the pre-submission enquiries is February 15, 2021, and the deadline for submission of the completed review articles is June 30, 2021.

Please send pre-submission inquiries to Assistant Editor Dr. Sandeep Kumar (skumarmabs@gmail.com) and Editor-in-Chief Dr. Janice Reichert (reichert.biotechconsulting@gmail.com), and contact us if you have any questions.

Filed Under: Antibody discovery Tagged With: antibody discovery, antibody therapeutics, bioinformatics

Antibody Discovery in the Cloud: Using NGS to expand the universe of selectable antibodies

January 13, 2021 by The Antibody Society

Registration for this free event is now open!

January 21 2021, 9am PST/12 ET/6pm CET

Speakers: Drs. Andrew Bradbury and M. Frank Erasmus (Specifica)

Antibody Discovery in the Cloud: Using NGS to expand the universe of selectable antibodies

The Specifica Generation 3 platform is able to generate 500-5000 different antibody clonotypes against targets of interest, with over 80% of selected antibodies having no measurable biophysical liabilities and 20% having subnanomolar affinities. The most common approach to selecting antibodies from display technologies involves low-throughput random colony screening. However, this missed many potential therapeutic leads, particularly when diversity is high. Specifica uses next generation sequencing (NGS) to build its libraries as well as characterize selection outputs. In order to fully exploit the universe of selectable antibodies, Specifica has developed a cloud-based software platform, designed exclusively for antibody engineers and bioinformaticians, to enable a streamlined identification of leads with broad epitope coverage. Application of this to selection outputs has increased the number of clonotype leads by five to ten fold over random colony screening, significantly expanding the explorable paratope space.

Click here to register!

Filed Under: Antibody discovery Tagged With: antibody discovery, next-generation sequencing

In memoriam: Jefferson Foote

December 23, 2020 by The Antibody Society

Written by:
E. Sally Ward (a), Peter Jones (b), Tim Buss (c), Cristina Rada (d), Gregory Winter (e) and Richard Willson (f)

a Centre for Cancer Immunology, University of Southampton, Southampton, UK
b Lode, Cambridge, UK
c Proteogenomics Research Institute for Systems Medicine, San Diego, USA
d MRC Laboratory of Molecular Biology, Cambridge, UK
e Trinity College, Cambridge, UK
f Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX, USA

Photo courtesy of Kathleen Foote.

Jefferson (Jeff) Foote sadly passed away of pancreatic cancer on January 17, 2020 at the age of 64.  He was a leading figure in physical immunochemistry and antibody humanization, a polymath of broad interests, and a wonderful friend and colleague.  Jeff was born in Chicago and grew up in Tarrytown, NY. Following graduation from Harvard University where he worked in the laboratory of William Lipscomb, he earned his Ph.D. at Berkeley with Howard Schachman, studying the canonical aspartate transcarbamylase system.  In 1985 he moved to the Laboratory of Molecular Biology (LMB) in Cambridge, where he worked with (now Sir) Greg Winter and then with Cesar Milstein. During his time in Cambridge, Jeff applied his understanding of protein biophysics and interaction kinetics to address problems in immunochemistry, increasingly leveraging the availability of the first emerging crystal structures of antibody-antigen complexes. This was before the BIAcore/surface plasmon resonance era that started in the early 1990s, and the work required a comprehensive knowledge of the inner workings of fluorometers, including stop-flow, and the associated mathematical tools. Jeff imported a Macintosh (“Mac”) culture to the laboratory, which was well-received by other local Mac fans in days when benchtop computers were still something of a novelty and there was a threat of other personal computer models becoming the norm.

Whilst at the LMB, Jeff made significant contributions in areas ranging from state-of-the-art antibody engineering to fundamental aspects of B cell biology, including the first description of the CDR grafting, or humanization, of an antibody specific for a hapten.[1] Jeff applied his expertise to determine the affinities of the test grafts, enabling the design principles of the engineered antibodies to be verified in precise, quantitative terms. This seminal study formed the foundation for the subsequent avalanche of therapeutic antibody humanizations, the first of which was the CD52-specific antibody Campath-1 (Alemtuzumab) generated in the Winter/Waldmann laboratories and used to treat chronic lymphocytic leukemia and multiple sclerosis. In addition, Jeff used the first antibody to be structurally solved in complex with antigen, the anti-lysozyme antibody D1.3, to define how framework residue modifications could restore binding behavior close to that of the donor (rodent) antibody to a humanized antibody.[2] As well as the biophysical characterization of framework mutants, he was also the first to synthesize a “consensus” framework.[2,3]

In parallel to Jeff’s work on antibody humanization, he carried out an extensive analysis with Cesar Milstein on how the maturation of the immune response is accompanied by an increased on-rate of antibodies for binding to their antigen. This study led to the paradigm that the selection of the “fittest” B cells is driven by interaction kinetics.[4] Subsequently, in a second publication with Cesar, Jeff observed that antibodies could undergo switching between different conformations (“conformational isomerism”), resulting in bi- or triphasic interaction kinetics.[5] This not only provided a molecular mechanism for the further diversification of antibodies, but also challenged the longstanding axiom that each lymphocyte produces an antibody with a single combining site.

Jeff was one of those more civilized members of the LMB who drove into work, rather than arriving with the appearance of a half-drowned rat following a cycle ride in the wintry, wet days that were common in Cambridge. Whilst working with Greg Winter in the tiny 5-6 person laboratory known as T4, Jeff relished being in the thick of the day-to-day, frequently frenetic activities. The day usually started with copious quantities of “Java”, an almost toxic, viscous dark brown liquid that kept the group members charged and running. Given that antibody humanization and, subsequently, antibody repertoire work were ongoing in the laboratory at this time, there was rarely a dull moment.

[Read more…]

Filed Under: Antibody discovery, Jeff Foote Tagged With: antibody discovery, antibody engineering

Fighting the Forever-war Against Infectious Diseases

September 16, 2020 by The Antibody Society

Author: Nick Hutchinson, Mammalian Cell Culture, Business Steering Group Lead, FUJIFILM Diosynth Biotechnologies (nick.hutchinson@fujifilm.com)

The COVID-19 crisis has had a devastating impact on populations across the world and caused the death of hundreds of thousands of people. The Antibody Society spoke to Dr. Jacob Glanville, CEO and President of Distributed Bio, Inc. to learn how his company has approached the development of new antibody therapeutics against the SARS-CoV-2 Coronavirus. He described how the crisis has stimulated innovation that may revolutionize the way we approach antibody discovery and development once the current pandemic is under control.

Dr Glanville explained, “The problem, when we think of every major outbreak, such as Ebola, SARS, MERS, Swine Flu, Avian Flu, is that the time it takes to develop a new drug is too long compared to the speed with which we need it. De novo discovery is too slow.”

To develop antibody therapeutics against COVID-19 as quickly as possible, Distributed Bio identified anti-SARS antibodies from almost 20 years ago that researchers had already shown would neutralize the SARS virus in vitro, protect mice from lethal challenge, and had known crystal structures. These antibodies have been studied extensively but were eventually too late to have an impact on the SARS crisis of 2003. It was Glanville’s idea to take advantage of the detailed functional research already performed on these antibodies and, try to retrofit them to bind to the new version of their original target the virus SARS-CoV-2. For this purpose, Distributed Bio applied their Tumbler technology, a computationally-guided antibody optimization method, capable of producing a library of billions of variants of individual antibodies exploring variations of all six complementarity-determining regions simultaneously.

“The novel coronavirus has around 74% homology in identity with the SARS receptor binding domain. I knew exactly how similar they were to the novel coronavirus as we had crystal structures of the SARS epitope. I believed that if we took five anti-SARS antibodies, there was going to be a pretty good chance that we would be able to adapt them to be a potent medicine against COVID-19,” said Glanville. “We already knew that they had the correct function, that they bound the right epitope in the right orientation with the right elbow angles. I believed that we could optimize them and enhance their affinity by making billions of versions of the antibodies within the library,” he continued.

According to Glanville, this is crucially important because historically, with outbreaks such as Ebola, the first antibodies launched were essentially prototypes with low potency or had inferior characteristics such as poor thermostability. It was the best-in-class not the first antibody that was successful, ultimately.

Distributed Bio were able to adapt all five antibodies in just nine weeks, a testament to the remarkable speed of these novel technologies. They sent a set of the most promising candidates to five laboratories which independently confirmed their ability to bind to the new SARS-CoV-2. The company then selected the two most potent antibodies for in-vivo testing, and two laboratories confirmed independently that both candidates protected healthy, as well as immuno-compromised animals using hamster models.

[Read more…]

Filed Under: Antibody discovery, Antibody therapeutic, Coronavirus, COVID-19 Tagged With: antibody therapeutics, SARS-CoV-2

Antibody Engineering & Therapeutics Europe Poster Competition Winners Announced!

August 7, 2020 by Janice Reichert

Congratulations to our winners!

To recognize the research activities of promising student and postdoctoral attendees of Antibody Engineering & Therapeutics Europe, The Antibody Society sponsors a competition for 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 research and development.

This year, our judges selected one student and one postdoc winners who receive: 1) complimentary registration to all conference sessions; 2) an opportunity to give a short oral presentation of their work in one of the conference sessions; and 3) a lovely crystal award.

The winners of the contest are:

Ms. Monica Fernandez-Quintero (University of Innsbruck)
Poster title: Antibodies exhibit multiple paratope states that can differ in VH-VL domain orientations

Dr. Christian Fercher (University of Queensland)
Poster title: Development of Reagentless Fluorescence Immunosensors for Continuous Analyte Monitoring

Please join us for the virtual Antibody Engineering & Therapeutics Europe conference on August 24-27, 2020.

Society members receive a 15% discount on the registration fee. Contact us at membership@antibodysociety.org for the code.

Filed Under: Antibody discovery, Antibody therapeutic, Award for Excellence Tagged With: antibody therapeutics

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