2017 Archived Content
The antibody engineering field is at an exciting stage of development, with new therapeutic concepts ranging from therapeutic cancer vaccines to TCR and checkpoint inhibitors promising access to and modulation of novel targets and pathways. Engineers
and protein scientists are eager to apply genomics, bioinformatics, and high throughput profiling techniques for antibody generation and discovery, and to improve the targeting and bioactivity of antibody therapeutics. At the 2nd Annual Engineering Antibodies at PEGS Europe, we invite scientists and engineers working in the field to share case studies and to-be-published work with us to inspire the next generation of antibody engineering.
Final Agenda
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WEDNESDAY 15 NOVEMBER
07:45 Registration and Morning Coffee
08:30 Chairperson’s Remarks
Jonas Schaefer, Ph.D., Head, High-Throughput Binder Selection Facility, Biochemistry, University of Zurich
08:35 KEYNOTE PRESENTATION: The Human Protein Atlas and Next Generation Antibody Therapeutics
Johan Rockberg, Ph.D., Assistant Professor, Proteomics and Nanobiotechnology, KTH Royal Institute of Technology
We have classified all the protein coding genes in humans using a combination of genomics, transcriptomics, proteomics and antibody-based profiling and used this data to study the global protein expression patterns in human cells, tissues and organs.
A Tissue Atlas was launch in 2015, a Cell Atlas in 2016 and a Pathology Atlas will be launched in 2017. This open access knowledge-base can be used to explore targets for next generation antibody therapeutics.
09:05 IgA as Novel Isotype to Treat Cancer
Jeanette Leusen, Ph.D., Associate Professor, Laboratory for Translational Immunology, University
Medical Hospital Utrecht
- IgA employs different effector mechanisms compared to IgG
- IgA both for solid and hematological tumors in preclinical models
- Half-life enhancement by glycoengineering and FcRn targeting
09:35 Alphabodies: A Novel Class of Biologicals Acting on Intracellular Targets
Yvonne McGrath, Ph.D., CSO, Complix NV
Many attractive intracellular targets involved in disease remain beyond the reach of conventional small molecules. We will describe the development of Alphabodies, a novel class of biologics that has been designed to enter cells effectively and
interfere with key intracellular pathways. Data showing target binding, functional interference and results from animal models will be exemplified.
10:05 An Integrated Approach to Managing Immunogenicity Risk and Drug Immune Modulation
Jeremy Fry, D.Phil., Director, Sales, ProImmune
Immunogenicity is one of the most complex issues to address in drug design and development. Using case studies to illustrate, I will provide a comprehensive overview of the most appropriate tools to mitigate immunogenicity risk, including Mass
Spectrometry antigen presentation assays; DC-T and T cell proliferation assays for biologic lead selection/optimization; HLA-peptide binding assays to characterize individual epitopes as well as undiluted whole blood cytokine storm assays.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 Recombinant Antibody Brain Shuttles - Improved Immunotherapy and Diagnostics of Neurodegenerative Diseases
Greta Hultqvist, Ph.D., Assistant Professor, Pharmaceutical Biosciences, Uppsala University
The blood brain barrier (BBB) hinders large molecules like antibodies to enter the brain and hence impedes immunotherapy and diagnostics of brain diseases. We have developed a symmetric BBB shuttle that transports antibodies across the BBB.
It increases the uptake at diagnostic doses almost 100 times and at therapeutic 10 times. We have used this shuttle with an antibody that binds to the amyloid fibrils in Alzheimer’s disease, and evaluated its performance as a therapeutic
and diagnostic marker.
11:45 A Bispecific Antibody Mimetic of FGF21 for the Treatment of Type 2 Diabetes
James A. Ernst, Ph.D., Senior Scientist, Protein Science, Genentech, Inc.
This talk will describe the discovery of an antibody that binds Klotho-Beta and FGFR1, thereby stimulating the cognate FGF21 co-receptor complex in adipose tissues. The selection of the receptor targeting arms will be described, and a
mechanism of activation of this receptor-complex is proposed. In addition, a catabolic mechanism of FGF21 inactivation in serum by the Fibroblast Activation protein will be described and implications of this inactivation for recombinant
and endogenous FGF21 discussed.
12:15 The Engineering of a HIV-1 Vaccine
Fernando Garces, Ph.D., Scientist, Molecular Engineering, Therapeutic Discovery, Amgen
Previous data has suggested that the Env protein is the most immunogenic when in its pre-fusion state making it paramount to favor this conformation in the designing of a vaccine capable of triggering a broad and potent immune response.
Here we present the first high-resolution crystal structures of this viral spike in complex with anti-HIV antibodies and how this molecular information provides a rational platform for intensive engineering. The immunogenic properties
of these native like trimer are currently being tested in a variety of animal models with promising results.
12:45 BioXp™ 3200 System for Flexible DNA Variant Library Construction
Ramon Espinoza-Lewis, Ph.D., Application Scientist, Product Development,
Synthetic Genomics
The synthesis of mutant genes is a labor-intensive and costly process, especially for the synthesis of variant libraries. This highly specialized and specific process is often outsourced to specialized service labs, increasing cost
& time with variable quality. Here, we describe the BioXpTM 3200 System, which enables researchers to engineer DNA in a highly flexible manner by introduction, deletion, or mutation of single nucleotides or fragments for production
of antibody segments, variant peptides or libraries.
13:15 Luncheon Presentation: Immunogenicity Assessment & Management – A Critical Part of a Holistic Approach to Successful Biologic Drug Design
Campbell Bunce, Ph.D., Senior Vice President, Scientific Operations, Biology, Abzena
Understanding how therapeutic antibodies and proteins can induce an immune response in patients leading to the development of anti-drug antibodies (ADAs) Accurate and sensitive ways to assess the potential immunogenicity of proteins
and antibodies ex vivo by measuring CD4+ T cell responses; Impact of functional properties of drug on selection of best ex vivo assay method to evaluate immunogenicity potential; Methods for managing and reducing potential immunogenicity.
13:45 Session Break
14:00 Chairperson’s Remarks
Jeanette Leusen, Ph.D., Associate Professor, Laboratory for Translational Immunology, University Medical Hospital Utrecht
14:05 Unique Properties of Mouse IgG
Joanna Bereta, Ph.D., Associate Professor, Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, The Jagiellonian University in Krakow
Contrary to the current belief that only IgMs are able to agglutinate erythrocytes, we obtained agglutinating mouse IgG3 that recognized antigen B of the human ABO blood group system. The high stability and production efficacy
of IgG3 point to this molecule as a potent diagnostic tool. Mouse IgG3s efficiently neutralize pathogens with a polysaccharide envelope or carbohydrate-rich cell wall. However, the receptor specific for IgG3, which could participate
in IgG3-based pathogen elimination, remains undiscovered; the results of our search for this high-affinity receptor will be presented.
14:35 A Systematic Approach for Peptide Characterization of B-Cell Receptor in Chronic Lymphocytic Leukemia
Manuel Fuentes, Ph.D., Scientist, Medicine & Proteomics Unit, Cancer Research
Center, University of Salamanca
The profiling of Ig sequences (at both DNA and peptide levels) are of great relevance to developing targeted vaccines or treatments for specific diseases or infections. Thus, genomics and proteomics techniques (such as Next-Generation
Sequencing (NGS) and mass spectrometry (MS)) have notably increased the knowledge in Ig sequencing and serum Ig peptide profiling in a high-throughput manner. Herein, it is described an integrated approach for genomics and
proteomics data to sequence membrane-bound Ig presented in antigen specific B-cells.
15:05 HERA: A Human Endothelial Recycling Assay for Rapid Screening of FcRn-Mediated Rescue from Degradation
Jan Terje Andersen, Ph.D., Associate Professor & Group Leader, Immunology,
Centre for Immune Regulation, Department of Biosciences, Oslo University Hospital and University of Oslo
IgG and albumin have a remarkably long serum half-life of three weeks in humans, which is mainly due to an efficient FcRn-mediated pH-dependent recycling pathway. As these ligands are increasingly utilized as therapeutics, there
is an intense interest in engineering of their half-life. Here, I will discuss a novel in vitro human endothelial cell-based rescue assay (HERA) that can easily be used for preclinical screening
of FcRn-mediated rescue of engineered ligands.
15:35 Refreshment Break in the Exhibit Hall with Poster Viewing
16:15 A Mammalian Display Platform for Antibody Discovery and Engineering Using Immunogenomic Engineering
Sai Reddy, Ph.D., Assistant Professor, Biosystems Science and Engineering, ETH Zurich
In this presentation, I will show how we combine NGS-based analysis with a novel mammalian hybridoma display platform for antibody screening and discovery. Specifically, we use NGS to identify candidate antigen specific clones
from immunized repertoires. We then integrate these antibody clonal libraries into our hybridoma platform using CRISPR-Cas9 genome editing. Flow cytometry is then used to screen and isolate antigen-specific antibodies.
16:45 Mammalian Display for B- and T-Cell Receptor Discovery and Engineering
Marc van Dijk, Ph.D., Executive Director, Platform Technology, Agenus
Agenus has invented novel display technologies to discover and engineer BCRs and TCRs, and will showcase their development of lab assays and bioinformatics algorithms to determine TCR specificity and off target liabilities.
17:15 Problem-Solving Breakout Discussions (View All Breakout Discussions)
Half Life Extension Technologies
Moderator:Jan Terje Andersen, Ph.D., Associate Professor & Group Leader, Immunology, Centre for Immune Regulation, Department of Biosciences, Oslo University Hospital and University of Oslo
Droplet Microfluidics for Antibody Discovery
Moderator: Christoph Merten, Ph.D., Group Leader Microfluidics, European Molecular Biology Laboratory (EMBL)
- what kind of screens can be done on primary plasma cells from mice and humans?
- What are the specific advantages compared to other screening formats?
- How to get access to the technology?
Intracellular Penetration – Getting Molecules Into Cells
Moderator: Ulrich Brinkmann, Ph.D., Expert Scientist, Large Molecule Research, Roche Pharma Research & Early Development, Roche Innovation Center Munich
- Internalization and vesicular enrichment works, the challenge and objective is delivery to the cytoplasm or nucleus
- Coming from the outside - how to get proteins across at least one biological barrier?
- Cell penetrating antibodies and vesicular escape promoting entities, compatibility with targeting approaches?
- Engineering 'against nature' what about the probability to win that match?
18:15 Networking Reception in the Exhibit Hall with Poster Viewing
19:15 End of Day
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THURSDAY 16 NOVEMBER
08:00 Registration and Morning Coffee
08:30 Chairperson’s Remarks
Marc van Dijk, Ph.D., Executive Director, Platform Technology, Agenus
08:35 Application of Deep Mutational Scanning in Therapeutic Antibody Engineering
Patrick Koenig, Ph.D., Senior Scientist, Antibody Discovery, AbbVie Stemcentrx
Deep mutational scanning combines the selection of limited mutagenesis libraries with deep sequencing. Here, I will present how information on sequence-function relationships obtained by deep mutational scanning is
a powerful resource to guide the engineering of affinity, specificity and stability of potential therapeutic antibodies.
09:05 Efficient Mining of the Memory B Cell & Plasma Cell Repertoire – Next Generation Antibody Discovery
Dale Starkie, Senior Scientist, Antibody Discovery - Variable Region Discovery and Engineering, UCB Celltech
Here we describe the use of a number of cutting-edge antibody discovery technologies and assays to efficiently interrogate the memory B cell and the plasma cell repertoire of immunised animals and humans to identify
rare antibodies with desirable functional characteristics. At the heart of this platform lies single cell isolation strategies which include both micromanipulation methods and droplet microfluidics. We will
present case studies to demonstrate how we have applied them to discovery of antibodies against therapeutically-relevant targets.
09:35 MemoMAB: Gateway to Human Antibody Repertoires
Christoph Esslinger, Ph.D., CSO, Memo Therapeutics
AG
The human immune repertoire is expected to yield valuable insights into novel protective mechanisms active in infectious diseases, cancer and other diseases. The MemoMAB microfluidics-based HT-single cell platform
banks and displays authentic antibody repertoires from human donors in recombinant form making them directly accessible for immune repertoire analysis and antibody discovery using functional screening. MemoMAB
processes up to 1mio B cells and directly delivers clonal cell lines expressing recombinant human antibodies.
10:05 Case Reports on Production and Functional Characterization of IgA Antibodies and Bispecific Antibody Formats
Matthias Peipp, Ph.D., Professor Division, Stem Cell Transplantation and Immunotherapy,
Christian-Albrechts-University of Kiel
Peer Heine, Ph.D., Field Applications Scientist, MaxCyte
Monoclonal antibodies are widely used in the treatment of cancer patents. To date the IgG1 isotype is predominantly used in various applications. As an alternative to commonly applied IgG antibodies, IgA antibodies
and bispecific antibody derivatives represent promising classes of biological agents in cancer immunotherapy. For the preclinical evaluation of structure-function relationships and effector mechanisms triggered
by different antibody formats, significant amounts of recombinant proteins are required. Efficient transient transfection systems are a prerequisite for comparison of various potential candidate molecules in
parallel. Here, case reports of the functional characterization of IgA antibodies and different formats of bispecific antibodies produced by scalable flow electroporation are presented.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 Technological Developments for Improved High-Throughput Binder Screenings and Validations
Jonas Schaefer, Ph.D., Head, High-Throughput Binder Selection Facility,
Biochemistry, University of Zurich
While recombinant binder selection pipelines by now work in rather high-throughput, the screening of suitable affinity reagents and especially the validation of their essential features for the final applications
is still laborious and time-intensive. To optimize the efficiency of these processes, we have improved already existing and developed novel methods, combining chip-, SPR- and MS-technologies, to efficiently
test candidates e.g. for crossreactivity and specificity.
11:45 Droplet Microfluidics for High Throughput Antibody and Vaccine Screening
Christoph Merten, Ph.D., Group Leader, Microfluidics, Genome
Biology Unit, European Molecular Biology Laboratory (EMBL)
We have developed droplet-based microfluidic platforms that allow the direct screening of >1 million primary, non-immortalized plasma cells (optionally from humans) in a single experiment and also facilitate
assays for the effect of antibodies on target cells (e.g. modulating GPCRs). In a complementary approach, we use the technology to monitor the binding of neutralizing antibodies to single HIV particles, which
allows us to derive vaccine candidates with customized antigen properties (e.g. improved stability and accessibility).
12:15 Luncheon Presentation: Modular Library Fabrication Strategies Deliver a Rapid and Cost-Effective Multi Use Approach
Emily Leproust, CEO, Twist Bioscience
Twist Bioscience’s unique ability to synthesize large numbers of high quality oligonucleotides, combined with its proprietary molecular biology protocols, allows the fabrication of precise, high fidelity gene
mutant libraries.With a rapid and cost effective approach to library fabrication, Twist Bioscience enables antibody developers and protein engineers to alter and evolve library designs as-needed. This presentation
will focus on the quality of libraries generated utilizing Twist Bioscience’s proprietary molecular biology protocols and modular fabrication strategies.
13:00 Dessert Break in the Exhibit Hall with Poster Viewing
13:30 End of Engineering Antibodies
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