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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

AIRR-dedicated Issue in the journal Current Opinion in Systems Biology 

December 30, 2020 by jpburckert

Ramit Mehr edited an issue on Systems immunology & host-pathogen interaction Current Opinion on Systems Biology to which many AIRR-C scientists have contributed. The issue encompasses eight original articles on the following topics: 

  1. Development of adaptive immune cells and receptor repertoires from infancy to adulthood, (2) Antigen discovery tools for adaptive immune receptor repertoire research
  2. The adaptive immune receptor repertoire community as a model for FAIR stewardship of big immunology data 
  3. Tools for adaptive immune receptor repertoire sequencing 
  4. Beyond bulk single-chain sequencing: Getting at the whole receptor 
  5. Disease susceptibility genes hidden in plain sight? 
  6. Mining adaptive immune receptor repertoires for biological and clinical information using machine learning 
  7. T cell repertoire sequencing as cancer’s liquid biopsy—can we decode what the immune system is coding? 

Read all articles here: https://www.sciencedirect.com/journal/current-opinion-in-systems-biology/vol/24/suppl/C.

Filed Under: AIRR Community, Systems Immunology Tagged With: Adaptive Immune Receptor Repertoire Community

AIRR Community and PrecisionFDA COVID-19 Precision Immunology App-a-thon

December 28, 2020 by Pam Borghardt

The AIRR Community is helping to lead the PrecisionFDA COVID-19 Precision Immunology App-a-thon.  

This is part of the “precisionFDA Challenges” program, which is designed to engage and improve software that analyzes NGS (next generation sequencing data) through community challenges. There were 68 bioinformaticians pre-registered for the Precision Immunology Challenge, and more are expected to join as the app-a-thon continues.  These “citizen scientists” will form teams to design software that will make AIRR-seq data more available and accessible for immunologists to realize the promise of immunological big data for improved diagnostics and therapeutics in immunotherapy.

The Precision Immunology Challenge uses AIRR-seq repertoire data from COVID-19 patients downloaded from the AIRR Data Commons (VDJServer and iReceptor Public Archive) through the iReceptor Gateway. These data sets have been carefully chosen to include data on patient demography and clinical outcome in order to illuminate the relationship between personalized adaptive immunity molecular data and COVID-19 disease variables.

The AIRR Community Diagnostics Working Group published a blog post as part of this effort, explaining the possible uses of AIRR-seq data in the clinic in the near future.

The app-a-thon runs through February 2021 at which time the apps will be judged for usability, impact and innovation.

 

Filed Under: AIRR Community, COVID-19, Food and Drug Administration Tagged With: Adaptive Immune Receptor Repertoire Community

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

FDA approves ansuvimab-zykl for Ebola virus infection

December 21, 2020 by Janice Reichert

On December 21, 2020, the US Food and Drug Administration approved Ebanga (ansuvimab-zykl) for the treatment for Zaire ebolavirus (Ebolavirus) infection in adults and children. Ebanga had been granted US Orphan Drug designation and Breakthrough Therapy designations. Ansuvimab is a human IgG1 monoclonal antibody that binds and neutralizes the virus.

The safety and efficacy of Ebanga were evaluated in the multi-center, open-label, randomized controlled PALM trial. In this study, 174 participants (120 adults and 54 pediatric patients) with confirmed Ebolavirus infection received Ebanga intravenously as a single 50 mg/kg infusion and 168 participants (135 adults and 33 pediatric patients) received an investigational control. The primary efficacy endpoint was 28-day mortality. Of the 174 patients who received Ebanga, 35.1% died after 28 days, compared to 49.4% of the 168 patients who received a control.

Ebanga is the 12th antibody therapeutic to be granted a first approval in the US or EU during 2020.

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format.

Filed Under: Antibody therapeutic, Approvals, Food and Drug Administration Tagged With: ansuvimab, antibody therapeutics, approved antibodies, Food and Drug Administration

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