2015 Archived Content
Cambridge Healthtech Institute’s Second Annual
Display of Antibodies
Empowering Novel Biologics
2-3 November 2015
New technologies are poised to change the gold standard for display methodologies in identifying and isolating protein ligands with the potential to become therapeutic antibodies. The full spectrum from discovery to clinical applications will be covered.
Topics will include antibody discovery, library construction, targeting membrane proteins and intracellular targets, generating novel constructs including antibody-drug conjugates, bispecific antibodies and alternative scaffolds, and enhancements
in eukaryotic display. This meeting is an essential event for anyone working in the area of protein engineering. Join us in November to network with your peers and be inspired by progress in the field.
Final Agenda
Day 1 | Day 2 | Speaker Biographies | Download Brochure
: Unpublished Data | 
: Case Study
Monday, 2 November
12:00 Conference Registration
COMBINED KEYNOTE SESSION
13:40 PEGS Europe Team Welcome
13:45 Chairperson’s Opening Remarks
Darrell Sleep, Director, Novozymes Biopharma R&D
13:50 Protein Engineering for New Modes of Actions and New Targets
Andreas G. Plückthun, Ph.D., Professor & Director, Biochemistry, University of Zurich
Using different display technologies and structure-based engineering, the possibilities of hitting extra- and intracellular targets will be discussed, with an emphasis on extending the modes of action previously possible. The lecture will emphasise
the need for interdisciplinary approaches.
14:30 Targeting Ion Channels
Tristan J. Vaughan, Ph.D., Vice President, R&D, Antibody Discovery & Protein Engineering, MedImmune
Ltd.
Ion channels are complex integral membrane proteins that form a pore through which ions selectively pass down an electrochemical gradient. They are prominent components of the nervous system where they can mediate transduction across synapses. Hence,
certain channels represent good drug targets, especially for alleviating pain. Approaches will be described to target such ion channels with antibody-based drugs and a case study presented.
15:10 Current and Future Trends in Antibody Therapeutics
Paul W.H.I. Parren, Ph.D., Senior Vice President & Scientific Director, Preclinical Development & Research, Genmab
Targeted treatment using antibody therapeutics has proved successful in the development of meaningful treatments in diverse therapeutic areas. However, despite strong advances, many patients still fail to respond or become resistant to targeted treatment
and novel innovative approaches to improve therapy are therefore required. Genetic and chemical engineering of antibodies, fueled by recent molecular insights, is providing important opportunities for the development of more potent antibody therapeutics.
Examples from Genmab’s portfolio will be provided.
15:50 Refreshment Break in the Exhibit Hall with Poster Viewing
16:30 Chairperson’s Remarks
John McCafferty, Ph.D., Co-Founder, Director and CEO, IONTAS Ltd.
16:35 Yeast-Based Platform to Select Rare Specificities and High Affinity Antibodies
Trevor A. Wattam, Ph.D., Manager, Biopharm Discovery Group, GlaxoSmithKline
This talk will provide an overview of GSK experiences with Adimab’s yeast-based platform. It will provide an overview of the lead discovery processes. In addition a couple of case studies will be presented demonstrating the power of employing FACS-based
selection to identify rare specificities and select high affinity antibodies.
17:05
Construction and Use of Large Antibody Libraries in Mammalian Cells
John McCafferty, Ph.D., Co-Founder, Director and CEO, IONTAS Ltd.
Using nuclease-directed integration of antibody genes we have constructed large libraries in mammalian cells containing a single antibody gene/cell. This allows surface display of antibodies, including IgG formatted antibodies, on the cell surface. This
will permit the screening of millions of clones by flow sorting and provide information on both expression level and the extent of binding within the cell types used for antibody production.
17:35 Antibody Library Display on a Mammalian Virus: Combining the Advantages of Panning and Cell Sorting in One Technology
Ernest S. Smith, Ph.D., Senior Vice President, Research & Chief Scientific Officer, Vaccinex, Inc.
We have developed an antibody discovery platform that enables efficient mammalian cell based expression of a library of human antibodies in full length IgG format on the surface of a mammalian virus. Upon infection of mammalian cells the antibody is not
only incorporated into newly produced virus, it is also displayed on the surface of the host cell. This technology allows us to combine the advantages of virus panning and cell sorting into one technology.
18:05 Welcome Reception in the Exhibit Hall with Poster Viewing
19:05 End of Day One
Day 1 | Day 2 | Speaker Biographies | Download Brochure
Tuesday, 3 November
07:45 Registration and Morning Coffee
08:30 Chairperson’s Remarks
Kerry Chester, Ph.D., Professor, Molecular Medicine, University College London Cancer Institute
08:40 DNA-Encoded Chemical Libraries for the Isolation of High-Affinity Binding Ligands: An Alternative to Antibodies
Dario Neri, Ph.D., Professor, Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich)
The tagging of chemical compounds with DNA fragments, serving as amplifiable identification barcodes, allows the construction and screening of libraries of unprecedented size. The isolation of small organic ligands from DNA-encoded chemical libraries
facilitates drug discovery applications.
09:10
Deep Microfluidic Screening for Discovery of Rare Antibodies with Optimal Properties
William S. Somers, Ph.D., Vice President, Global Biotherapeutic Technologies, Pfizer
We are in a collaboration with HiFi Bio to establish a next generation microfluidic platform for antibody discovery that is allowing us to screen very large numbers of B-cells from humans and immunized animals for molecules that possess properties
of interest. The massive throughput of the instrument and information rich assays allow us to identify rare antibodies that have both the biological activity of interest and favorable manufacturing properties.
09:40 PROBLEM SOLVING ROUNDTABLE DISCUSSIONS
Table 1: The Role of in vivo Molecular Imaging in the Development of Immunotherapy
Moderator: Tammy L. Kalber, Ph.D., EPSRC Fellow, Metabolism & Experimental Therapeutics, Centre for Advanced Biomedical Imaging (CABI), University College London
- Multimodality imaging – discuss the range of preclinical modalities available, the pros and cons of each and how they can be used in synchrony to complement one another
- Cellular imaging – discuss state of the art methods for non invasive imaging of engineered T cells
- Protein and Antibody imaging – discuss state of the art methods for non invasive imaging of proteins and antibodies
Table 2: Comparison of Technologies: Hybridoma, Phage, Transgenics and the Kitchen Sink
Moderator: Jacob Glanville, Co-Founder and CSO, Distributed Bio Inc
Topics to be announced.
Table 3: Next-Generation Sequencing of Phage Display Panning Output Pools to Guide Antibody Lead Selection
Moderator: Stefan Ewert, Ph.D., Senior Investigator, NIBR Biologics Center, Novartis Pharma AG
- Which libraries and selection technologies could benefit from NGS?
- Which functional and biophysical properties of candidates could be assessed using NGS?
- How far can we go: Would it be possible to replace classical screening via ELISA?
10:40 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 Chairperson’s Remarks
Kerry Chester, Ph.D., Professor, Molecular Medicine, University College London Cancer Institute
11:20
Engineered T Cell Receptors as Tools for the Study of Peptide–MHC Interactions
Geir Åge Løset, Ph.D., Researcher, Centre for Immune Regulation and Department of Biosciences, University of Oslo; CSO, Nextera AS
The use of phage display as tool to evolve cloned T cell receptors represents an attractive avenue to generate reagents for mechanistic studies of native pMHC engagement. We have systematically looked into domain format variants and phage display
engineering to obtain such functional soluble T cell receptors allowing for a deeper disease mechanism elucidation within autoimmunity. In parallel, we have also developed alternative pMHC-targeting units by phage display.
11:50 Multiscale, Multimodal in vivo Imaging of CAR T Cell Therapies
Tammy L. Kalber, Ph.D., EPSRC Fellow, Metabolism & Experimental Therapeutics, Centre for Advanced Biomedical Imaging (CABI), University College London
Adoptive immunotherapy using chimeric antigen receptor (CAR) engineered T cells has shown promising results in treating various cancer types. In vivo imaging plays a key role in the development of CAR T cell therapies, allowing us to study their homing,
engraftment, expansion, persistence and demise longitudinally and non-invasively in animal and man. This talk will provide an overview of current state-of-the-art multiscale and multimodality imaging technologies available.
12:20 Screening and Charactersation of Biologics using a High Sensitivity Plate-based Laser Scanning Cytometer
Paul Wylie, Ph.D., Head, Instrumentation Applications Group, TTP LabTech Limited
The mirrorball fluorescence cytometer is applicable to many stages within biologics discovery from screening to identify hits to binding characterisation and monitoring phenotypic responses. Streamlined no wash cell or bead-based assays provide process
efficiencies over standard Flow or ELISA formats, enabling you to do more with precious samples and time.
12:35
Efficient Mammalian Cell Transfection for Antibody Discovery
Michael Dyson, CTO, IONTAS Ltd
Transfection of mammalian cells is important for therapeutic antibody discovery including antigen production and antibody expression for functional screening. A comparison of different transfection methods in CHO and HEK293 cells will be presented.
Transfection of mammalian cells has also been used to create libraries of antibodies displayed on the surface of mammalian cells and for the display of engineered T cell receptors.
12:50 Luncheon Presentation:Deep Sequencing
of Paired VH-VL Regions from in vitro Selection Assays
Chris Mozdzierz, Ph.D., Associate Manager, Next-Generation Sequencing, GENEWIZ
In this presentation, GENEWIZ's Chris Mozdzierz will discuss Deep Sequencing of Paired VH-VL Regions from in vitro Selection Assays. He will also discuss how innovative technologies such as GENEWIZ's FuzeSeq Antibody Sequencing can help overcome the
existing limitations of conventional NGS.
13:20 Session Break
14:00 Dessert Break in the Exhibit Hall with Poster Viewing
14:30 Chairperson’s Remarks
Gregory A. Weiss, Ph.D., Professor of Chemistry, Molecular Biology and Biochemistry, University of California, Irvine
14:35
Next-Generation Sequencing of Phage Display Panning Output Pools to Guide Antibody Lead Selection
Stefan Ewert, Ph.D., Senior Investigator, NIBR Biologics Center, Novartis Pharma AG
With the availability of bench-top personal sequencers it is now possible to apply Next Generation Sequencing (NGS) of Phage Display panning output pools during the antibody discovery process. Starting with a polyclonal 1.0E+06 Phage Display output
pool after 3 panning cycles followed by adapted panning conditions and NGS analysis, we have been able to predict cross-reactivity profiles and biophysical properties like melting temperature of antibody candidates. Ultimately, we aim to replace
classical screening methods and rely solely on adapted panning strategies followed by NGS to identify antibody leads out of the complete Phage Display output pool.
15:05
Call of the Wild: A New Generation of Antibody Discovery from Natural Sources
Jacob Glanville, Co-Founder and CSO, Distributed Bio Inc.
The integration of new immunological insights, phage indexing technologies, and seven years NGS algorithm development has armed new design principles to harvest antibodies from natural repertoires. First, we review modeled insights gained from attempting
to mimic nature by synthetic methods, with applications in in vitro SHM replacement and novel humanization technology. Next, we present a computationally-guided SuperHuman library built from natural sources. Finally, we describe a Survivor library
generated from the blood of an army of cancer survivors.
15:35 Phenotypic Screening for Novel Antibody Targets in the Tumour Microenvironment
Ralph R. Minter, Ph.D., Fellow, Antibody Discovery and Protein Engineering, MedImmune Ltd.
There is growing interest in finding and validating novel targets in the tumour microenvironment, especially in the burgeoning field of immunotherapy. We have been using phage display and phenotypic screening of antibodies to identify and validate
novel targets both on cancer cells and immune cells which infiltrate tumours. Examples will be given to demonstrate the advantages of phenotypic screening for the identification of targets and drug leads in this context.
16:05 Combining the Benefits of Immunized Libraries, in vitro Selections and Computational Design for Antibody Discovery
Vera Molkenthin, Ph.D., Chief Scientist, AbCheck s.r.o
Rabbits are known to produce high affinity and diverse antibodies even against difficult targets. A library-based method allows the humanization of the complete VH/VL sequence repertoire of an immunized rabbit in one batch and offers a new approach
to antibody discovery. The libraries are computationally designed for optimal developability properties, excluding T-cell epitopes and biochemical liabilities. Special strategies allow the selection of antibodies with slow dissociation rates,
species cross reactivity and high thermal stabilities.
16:35 Refreshment Break in the Exhibit Hall with Poster Viewing
17:10 Chairperson’s Remarks
Claire Dobson, Ph.D., Associate Director, Antibody Discovery & Protein Engineering, MedImmune Ltd.
17:15
Dissecting and Engineering Phage-Displayed Membrane Proteins
Gregory A. Weiss, Ph.D., Professor of Chemistry, Molecular Biology and Biochemistry, University of California, Irvine
Membrane proteins (MPs) control the cell’s communications, sensing and responses to extracellular events. Yet MPs most remain off-limits to conventional protein engineering. The Weiss laboratory has reported a new type of bacteriophage allowing
display and mutagenesis of this important class of proteins. The approach opens new frontiers to dissect and tailor binding by MPs and their binding partners. Several examples illustrating the power of the approach will be presented.
17:45 Computer-Guided Design of Antibodies Combined with Display Technologies to Identify Antibodies to Difficult Targets
Yanay Ofran, Ph.D., Founder, Biolojic Design Ltd.
Display technologies select for binding, not for activity. But the functional effect of an antibody is determined by the mode of binding, not only by the affinity. This talk will present a data-driven computational approach for designing of libraries
that can yield binders with a preselected mode of binding. It has shown success in designing antibodies against difficult targets as well as bi-specific antibodies.
18:15 Targeted Modulation of hERG Channel Activity with scFv Antibody Fragments
Carol A. Harley, Ph.D., Research Scientist, Structural Biochemistry, IBMC- Instituto de Biologia Molecular e Celular
The KCNH voltage-dependent potassium channels have key roles in diseases such as cardiac LQT2 syndrome, schizophrenia and cancer. The intracellular domains of the hERG ion channel are important for modulating it´s activation properties.
We have isolated and identified novel scFv antibodies that target specific regions within the N-terminal cytoplasmic domain of the hERG channel which modulate channel kinetics. This opens up a novel mode of ion channel modulation.
18:45 End of Display of Antibodies
Day 1 | Day 2 | Speaker Biographies | Download Brochure
: Unpublished Data | : Case Study