Cambridge Healthtech Institute’s Inaugural

Phage and Yeast Display of Antibodies

Empowering Novel Biologics

3-4 November 2014


Speaker BiographiesDownload Brochure | Register 

Phage and yeast display are the gold standard for identifying and isolating protein ligands with the potential to become therapeutic antibodies. Applications include antibody discovery, library construction, targeting membrane proteins and generating novel constructs including antibody-drug conjugates, bispecific antibodies and alternative scaffolds. Examples of the use of display technologies for intracellular and oncogenic targets will be addressed along with updates on the emerging area of in vivo selection of antibodies.


Monday, 3 November

12:00 Conference Registration


PLENARY SESSION 

13:45 PEGS Europe Team Welcome 

13:50 Chairperson’s Opening Remarks 

William Finlay, Ph.D., Director, Global Biotherapeutic Technologies, Pfizer, Inc. 

14:00 The Impact of the New Regulatory Guidance Landscape on the Validation of the Manufacturing Process and the Characterisation of Starting Materials, Drug Substance and Drug Product 

Steffen GrossSteffen Gross, Ph.D., Head, Monoclonal and Polyclonal Antibodies, Paul-Ehrlich-Institut 

The regulatory guidance landscape regarding biological products changes rapidly. Documents overseeing process validation is currently facing major overhauls. New guidelines are published defining the requirements for starting materials and excipients. This might have a deep impact not only on the process development of traditional monoclonal antibody type products but also on new antibody formats such as conjugates as well as on new developed formulations. 

14:45 Current Progress with Armed Antibody Products 

Dario NeriDario Neri, Ph.D., Professor, Chemistry and Applied Biosciences, ETH Zurich 

There is an emerging trend in Pharmaceutical Biotechnology to “arm” antibodies, capable of selective localization at the site of disease, with suitable therapeutic payloads (e.g., drugs, cytokines, radionuclides, a second antibody moiety, hence producing a bispecific product). This strategy aims at concentrating therapeutic agents in diseased part of the body, while sparing normal tissues. In this lecture, I will present a comparative evaluation of different classes of armed antibody products, developed in my laboratory in collaboration with Philogen. In particular, I will present preclinical and clinical data of armed antibodies in the field of cancer, of chronic inflammation and of endometriosis. 


15:30 Refreshment Break


OPENING SESSION

16:00 Chairperson’s Opening Remarks

John McCafferty, Ph.D., Co-Founder, Director and CEO, IONTAS Ltd.


16:05 Keynote Presentation:

Construction and Use of Large Antibody Libraries in Mammalian Cells

John McCaffertyJohn McCafferty, Ph.D., Co-Founder, Director and CEO, IONTAS Ltd.

Construction of libraries of binders displayed on the surface of mammalian cells will allow the screening of millions of clones by flow sorting while providing information on both the level of expression and the extent of binding within individual clones. The main limitation to achieving this has been the inability to construct large libraries containing 1-2 antibody genes/cell. We have solved this problem by directing the integration of antibody genes into a single genomic locus through the use of site-specific nucleases. The presentation will describe construction of libraries of millions of clones and selection of binders including antibodies formatted as IgGs.


16:35 Bench to Bedside: Taking Antibodies Derived from Phage Display to the Clinic

Kerry ChesterKerry Chester, Ph.D., Professor, Molecular Medicine, University College London Cancer Institute

The application of phage display technology to create and mine vast libraries of antibody fragments can provide a diversity of new binders from naive, immunised or synthetic repertoires. We have taken the approach of using PCR-mediated amplification of antibody V genes from immunised rodents as a source of V-regions; exploiting the single chain Fv (scFv) format, for display and as a building block for potential therapeutics. Selected scFv are readily converted into a variety of potential biotherapeutics, including antibody-enzyme fusion proteins, dual-specific binders, scFv-Fcs and Chimeric Antigen Receptors (CARs). Bench-to-bedside case studies will be presented.

17:05 Full-Length IgG Antibody Surface Display in Mammalian Cells

Josef Platzer, Ph.D., Senior Principal Scientist, Large Molecule Research,  Roche Diagnostics GmbH

Therapeutic proteins are currently evolving from standard monoclonal antibodies to more complex formats and fusion proteins. The display of antibody libraries is an important tool to identify the most potent hits. For complex formats a display in the final format is desirable. Here we report on a mammalian cell surface display for full length IgGs and bispecific antibodies.

17:35 Breakthrough Therapy: Targeting Therapeutic Specifically to Inflamed Arthritic Joints

Ahuva Nissim, Ph.D., Reader, Antibody and Therapeutic Engineering, Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London
 

18:20 Welcome Reception in the Exhibit Hall with Poster Viewing

19:20 End of Day One




Tuesday, 4 November

07:30 Registration

07:45 Morning Coffee


TACKLING COMPLEX MEMBRANE TARGETS WITH DISPLAY TECHNOLOGIES

08:30 Chairperson’s Remarks

Claire Dobson, Ph.D., Associate Director, Antibody Discovery & Protein Engineering, MedImmune

08:40 Isolating and Optimising Antibodies to Complex Membrane Targets

Claire DobsonClaire Dobson, Ph.D., Associate Director, Antibody Discovery & Protein Engineering, MedImmune

Isolating antibodies to G protein coupled receptors (GPCRs) is challenging due to their complex nature. This presentation will provide an overview of strategies adopted by MedImmune to successfully identify potent functional antibodies directed to these complex membrane targets.

09:10 Development of Conformation-Selective Antibodies by Yeast Display

Bradley PearseBradley Pearse, Ph.D., Scientist II, Antibody Discovery, Biogen Idec

Generating antibodies that are able to distinguish between active and inactive conformations of integrins is of great therapeutic interest. In this presentation, the discovery of conformation-selective human antibodies using yeast surface display will be discussed. The focus will be on the design of selection strategies to enrich antibodies of interest by yeast display and characterisation of conformer selectivity. Examples of conformationally-selective non-ligand mimetic antibodies will be highlighted in greater detail.

09:40 Development of Potent and Selective Nanobodies against Difficult Targets: Tackling GPCRs and Ion Channels

Gerald BesteGerald Beste, Ph.D., Associate Director, Discovery, Ablynx

Nanobodies® are therapeutic proteins based on single-domain antibody fragments derived from naturally occurring heavy-chain only antibodies from camelids. They can be easily engineered via genetic fusion into multi-valent and multi-specific molecules. Case studies on how this formatting flexibility can be exploited for the generation of potent and selective biologicals against GPCRs and ion channels will be presented.

10:10 Coffee Break in the Exhibit Hall with Poster Viewing

10:50 Discovery of Rare Antibody Specificities to Difficult Targets Using High Content Screening of Avian Repertoires

William D. Harriman, Ph.D., CSO & Founder, Crystal Bioscience

Chickens are known to generate antibodies to epitopes on therapeutic targets that are highly conserved amongst mammals. These antibodies often demonstrate reactivity across multiple species, and are preferred when rodent or primate models of disease are anticipated. Using alternative immunization strategies we can enhance the prevalence of such clones, and by evaluating antibody profiles through a multi-parameter GEM screen of primary B cells, we can efficiently recover antibodies with desired biological activity and/or multispecies cross-reactivity.

11:20 High-Throughput Design, Production, and Evaluation of Bispecific Antibodies

Maria Wendt, Ph.D., Senior Scientific Consultant, Biologics, Genedata

Work on multispecific antibodies has exploded and more sophisticated engineering approaches are now used. Concurrently, increasing numbers of bispecific platforms (e.g. tandem-scFv-Fc, DVD-Ig, diabodies) and parametric variants (e.g. linkers, V-domain orientation, Fc) must be tested. We present latest advances in our workflow platform for fully automated molecule design, DNA synthesis, and verification. Integrated into a comprehensive data management system for samples, assays, and analytics results, it enables systematic evaluation of large panels of next-generation antibodies.


11:50 Problem Solving Roundtable Discussions

The Selection, Screening and Characterisation of Bispecifics

Moderator: Christopher J. Plummer, Ph.D., Scientific Investigator, Biopharm Innovation, GlaxoSmithKline

  • Maximizing the diversity of selection outputs
  • Determining Epitope coverage
  • Benefits of different screening methodologies

Complex Membrane Targets

Moderator: Claire Dobson, Ph.D., Associate Director, Antibody Discovery & Protein Engineering, MedImmune

  • Challenges of isolating antibodies to GPCRs
  • Strategies to identify potent functional antibodies
  • Examples on complex membrane targets

How to Get What You Want from Antibody Phage Display

Moderators: Stefan Dübel, Ph.D., Professor, Biotechnology, Technical University of Braunschweig

and John McCafferty, Ph.D., Co-Founder, Director and CEO, IONTAS Ltd.
 

  • Immunized vs. universal libraries?
  • How to set up a panning strategy to optimise success
  • How to improve results with "difficult" targets
  • Phage display approaches
  • Potential for high throughput antibody generation
  • Affinity maturation
  • Creation of libraries
  • Examples
 

 

12:50 Luncheon Presentation: Antibody Library Display on a Mammalian Virus: Combining the Advantages of Panning and Cell Sorting in One Technology

Smith_ErnestErnest S. Smith, Ph.D., Senior Vice President, Research & CSO, 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 vaccinia 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 enables a selection method that combines the advantages of virus panning and cell sorting into one technology.

14:00 Dessert Break in the Exhibit Hall with Poster Viewing


GENERATING ADCs, BISPECIFIC ANTIBODIES AND NOVEL SCAFFOLDS

14:30 Chairperson’s Remarks

Kerry ChesterKerry Chester, Ph.D., Professor, Molecular Medicine, University College London Cancer Institute






14:35 Selection, Screening and Characterisation of Bispecific “mAb-dAbs”

Christopher J. Plummer, Ph.D., Scientific Investigator, Biopharm Innovation, GlaxoSmithKline

This talk will provide an overview of the process involved for the lead discovery of bispecific mAb-dAbs, detailing the methods of selection, screening and characterisation to identify bispecific molecules with suitable biological, biophysical and pharmacokinetic properties for therapeutic use.

15:05 The Cyclotide Microprotein Family as a Scaffold for Drug Discovery and Delivery

Bill EldridgeBill Eldridge, Ph.D., CSO, Cyclogenix Ltd.

Cyclotides, or knottins, are plant-derived cystine knot microproteins (CKMs). Despite their very high structural rigidity there is great sequence diversity within this family. We have therefore substantially modified the wild type primary sequence and used to phage display to select mutated CKMs which demonstrate a range of modalities, including oral availability, traditional protein target-specific binding and the possibility of blood-brain barrier delivery of therapeutic peptides. Specific examples will be discussed.

15:35 Advancing Novel Bispecific Antibody Biologics

Jose M. Munoz-OlayaJose M. Munoz-Olaya, Ph.D., Scientist, Discovery, F-star Biotechnology Ltd.

F-star has developed a novel modular bispecific antibody technology. First, Fcab™ or antigen-binding Fc heavy chain (CH3) domains are selected using proprietary phage or yeast display technology. Next, bispecific mAb²™ antibodies can quickly and easily be expressed by replacing the wild-type Fc domain of existing monoclonal antibodies. F-star is now developing a preclinical oncology pipeline based on this next generation biologics technology platform.

16:05 Sponsored Presentation (Opportunity Available)

16:35 Refreshment Break in the Exhibit Hall with Poster Viewing


CHIMERIC ANTIGEN RECEPTORS (CARS)

17:15 Novel Targeting Concepts in CAR Technology

Martin PuleMartin Pule, Ph.D., Clinical Senior Lecturer Honorary Consultant, Haematology, University College

In order to resolve the “on target off tumour” toxicity in CAR therapy we developed logic gate platforms that can engineer T cells to either broaden their specificity to more than one phenotype of cancer (OR gate platform) or to specifically recognise cancerous cells in the absence of cancer specific antigens (AND and ANDNOT gate platform). This was achieved by transducing T cells with two modified CARs which, depending on the target cell phenotype and platform, resulted in the co-operative or destructive integration of ligated signals.

17:45 Preclinical Engineering and Clinical Evaluation of First Generation CAR T-Cells Employing a Phage Display-Derived scFv against Carcinoembryonic Antigen (CEA)

David GilhamDavid Gilham, Ph.D., Senior Research Fellow, Clinical and Experimental Immunotherapy Group, Institute of Cancer Sciences, University of Manchester

A key limitation of Chimeric Antigen Receptor (CAR) T-cell technology is the availability of a suitable antibody scFv fragment that functions in the CAR format. This talk will explore the engineering issues and clinical grade cell production issues relevant to using a phage display generated scFv specific for CEA in a first generation CAR format and the testing of these gene-modified T-cells in a phase I clinical trial setting.


IMPROVING BIOPHYSICAL PROPERTIES

18:15 Expression of IgG in Mammalian Cells Directly from Phage Display Vectors without Subcloning

Isidro HötzelIsidro Hötzel, Ph.D., Senior Scientist, Antibody Engineering, Genentech

Phage display is widely used in discovery of therapeutic antibodies. A bottleneck in the screening of clones from phage display libraries is the subcloning of variable regions to mammalian vectors for expression of IgG. We developed a vector for phage display that expresses IgG in mammalian cells without reformatting, expediting the screening of clones derived by phage display.

18:45 End of Phage & Yeast Display of Antibodies



Speaker BiographiesDownload Brochure | Register