phage display new classes of therapy

The Sixth Annual Display of Biologics track at PEGS Europe has showcased technologies and visionaries in the field of biologics. Molecular evolution using the tools of phage, yeast, bacterial and other display methods have yielded a staggering array of bispecific antibodies, antibody-drug conjugates, immunotherapies and other constructs. The emergence of CRISPR for genome editing, deep sequencing, machine learning, AI and computational tools will be applied to improve design and efficacy of candidates.

Final Agenda

Scientific Advisory Board

Ana Barbas, PhD, Coordinator, Bayer Satellite Laboratory at iBET, iBET and Bayer Portugal SA

David Lowe, PhD, Senior Director, R&D, Antibody Discovery and Protein Engineering, AstraZeneca

Ahuva Nissim, PhD, Professor, Antibody and Therapeutic Engineering, William Harvey Research Institute, Queen Mary University of London

Recommended Short Course*

SC1: Advanced Introductory Course on Making Antibody Libraries in Phage and Yeast - LEARN MORE

*Separate registration required.


12:00 Conference Registration (Foyer A)

Auditorium VII

13:30 Organiser’s Welcome

Christina Lingham, Executive Director, Conferences & Fellow, Cambridge Healthtech Institute

13:35 Chairperson’s Opening Remarks

Nissim_AhuvaAhuva Nissim, PhD, Professor, Antibody and Therapeutic Engineering, William Harvey Research Institute, Queen Mary University of London

13:45 Using Phage Display and Computational Approach to Dissect Structural Determinants of Celiac Disease Autoantibodies

Sblattero_DanieleDaniele Sblattero, PhD, Professor, Dipartimento Scienze della Vita, Università degli Studi di Trieste

Characterization of antibody repertoires is essential for understanding disease mechanisms involving humoral Ag-specific auto-immunity. Here we describe the construction and selection of antibody fragment libraries from celiac disease (CD) patients. Selected antibodies to tissue transglutaminase (TG2), a hallmark of CD, show a striking bias in VH and VL gene usage with clear preferences in pairing. By applying computational analyses based on selected Abs, we were able to successfully design in silico a synthetic TG2-directed Abs.

14:15 A New Phage Display Vector Allowing Direct Screening in IgG Format

Martineau_PierrePierre Martineau, PhD, Deputy Director, Functional Screening and Targeting in Cancer, Institut de Recherche en Cancérologie de Montpellier, Inserm, Université de Montpellier - ICM

Display methods are restricted to antibody fragments and based on binding activity. However, the preferred format for therapeutic applications is the IgG, whose binding properties are affected by reformatting but also engages the immune system by its Fc part. We thus developed a display vector and an engineered mammalian cell line that allow both phage display and direct generation of cells stably secreting a monoclonal human IgG for functional screening.

14:45 A Novel scFv Antibody Fragment to Misfolded Alpha Synuclein as a Potent Modulator of Neuroinflammation by in vivo Intransal Delivery

George_JacobJacob George, MD, Founder, Cognyxx

A scFv (CGX208) that was cloned from Fab phage display libraries binds preformed fibrils and short alpha synuclein(aSyn) oligomers. CGX208 exhibited avid binding to brain extracts from patients with synucleinopathies. Intranasal delivery of CGX208 results in a significant attenuation of neuroinflammation driven by misfolded aSyn and is effective in ameliorating motoric dysfunction in different in vivo experimental Parkinson’s Disease models. CGX208 may prove a novel promising agent to treat aSyn medicated neuroinflammation.

15:15 Streamlined Discovery and Production of Therapeutic Antibodies

Lauri Peil, Key Account and Technology Officer, Icosagen

We take advantage of the universal HybriFree antibody discovery engine to efficiently discover therapeutic antibodies by direct cloning from B cells of immunized rabbit, chicken, human, or dog. HybriFree method is further powered by our patented QMCF expression platform to produce high-quality recombinant protein antigens, and antibodies cost-effectively for preclinical research (including afucosylated antibodies for enhanced ADCC). Technologies and case studies will be presented and discussed.

15:45 Networking Refreshment Break (Foyer D)

Auditorium I

16:15 Moderator’s Opening Remarks

Kerry Chester, PhD, Professor, Molecular Medicine, University College London Cancer InstituteKerry Chester, PhD, Professor, Molecular Medicine, University College London Cancer Institute






16:20 Bispecific, Soluble TCR as the Next Therapeutic Platform

Bahija Jallal, PhD, CEO and Director of the Board, ImmunocoreBahija Jallal, PhD, CEO and Director of the Board, Immunocore

Of the two adaptive immunity recognition motifs, only antibodies have been brought to patients. However, antibody therapeutics only recognize 10% of human proteome (surface-expressed). The other motif, T cell receptor (TCR), has potential to unlock 90% of the human proteome, but requires converting a low-affinity, specificity membrane receptor into a soluble therapeutic. IMCgp100, a soluble, TCR bispecific-targeting melanoma, is the most advanced soluble TCR therapeutic in development.

17:20 Attacking Cancer Cell Surfaceomes with Recombinant Antibodies

James A. Wells, PhD, Professor, Departments of Pharmaceutical Chemistry and Cellular & Molecular Pharmacology, University of California, San FranciscoJames A. Wells, PhD, Professor, Departments of Pharmaceutical Chemistry and Cellular & Molecular Pharmacology, University of California, San Francisco

The cell surface proteome (surfaceome) is the primary hub for cells to communicate with the outside world. Oncogenes are known to cause huge changes in cells and we find this translates to significant remodeling of the surfaceome. We generate recombinant antibodies to detect and then attack these cells by toxifying the antibodies or recruiting immune cells to kill. I’ll discuss the technologies for surface protein analysis, an industrialized platform for rapid antibody generation using phage display, and using these tool reagents for target validation.

Abcam 18:20 Welcome Reception in the Exhibit Hall with Poster Viewing (Rio Pavilion)

19:30 End of Day


07:45 Registration(Foyer A) and Morning Coffee (Foyer D)

08:30 Chairperson’s Remarks

Lowe_DavidDavid Lowe, PhD, Senior Director, R&D, Antibody Discovery and Protein Engineering, AstraZeneca

08:35 KEYNOTE PRESENTATION: Antibodies with Affinity Switches

Duebel_StefanStefan Dübel, PhD, Professor & Chair, Technische Universität Braunschweig, Institute of Biochemistry, Biotechnology and Bioinformatics

Using cyclic mutants of human calmodulin as an allosteric effector module, antigen-binding affinity of various antibodies could be regulated. This allosteric effect was demonstrated for five different scFv fragments under physiological conditions without the need of pH or ion concentration changes. Antibodies could be both switched on or off, and the switch worked with the antibodies bound to living cells. Therefore, this approach may provide a universal strategy to obtain affinity-switchable antibodies without the need for individual paratope engineering, and to use these to fine-tune any immunomodulatory effect.

Auditorium VII


09:05 High-Throughput Antibody Engineering in Mammalian Cells by Homology-Directed Mutagenesis

Reddy_SaiSai Reddy, PhD, Associate Professor, Department of Biosystems Science & Engineering, Laboratory for Systems and Synthetic Immunology, ETH Zurich

We have recently established a technique known as homology-directed mutagenesis (HDM), which is able to generate mutagenesis libraries directly in mammalian cells using CRISPR-Cas9. In HDM, we introduce genetic diversity into the genome of antibody-expressing cells by using site-specific or random mutagenesis DNA donor templates, which are integrated after Cas9 targeted double-stranded breaks. HDM enables several of the most essential methods of antibody engineering to be performed directly in mammalian cells expressing full-length IgG. This includes generation and screening of synthetic libraries for antibody discovery and affinity maturation.

09:35 Problem-Solving Breakout Discussions

TABLE 1: Emerging Technologies for High Throughput Antibody Discovery

Moderator: Thomas Bouquin, PhD, Head, Biologics Research France, Centre de Recherche de Vitry/Alfortville, Sanofi

  • Microfluidics
  • Engineering of antibody using eukaryotic display technologies


TABLE 2: Synthetic vs. Natural Diversity in Antibody Libraries

Moderator: Pierre Martineau, PhD, Deputy Director, Functional Screening and Targeting in Cancer, Institut de Recherche en Cancérologie de Montpellier, Inserm, Université de Montpellier – ICM

  • Repertoire diversity
  • Affinity of clones
  • Epitope coverage
  • Developpability of obtained mAbs
  • Immunogenicity
  • Currently registered mAbs origin

10:30 Coffee Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)

Auditorium VII

Chairperson’s Remarks

David Lowe, PhD, Senior Director, R&D, Antibody Discovery and Protein Engineering, AstraZeneca

11:15 SAMURAI (Solid-Phase Assisted Mutagenesis by Uracil Restriction for Accurate Integration) – A Method for Generation of High-Quality Antibody Libraries

Rockberg_JohanJohan Rockberg, PhD, Assistant Professor, Protein Science, KTH Royal Institute of Technology

Mutagenesis libraries are essential for combinatorial protein engineering. Despite improvements in gene synthesis and directed mutagenesis, current methodologies still have limitations regarding the synthesis of complete antibody single-chain variable fragment (scFv) genes and simultaneous diversification of all six CDRs. Here, we present the generation and use of mutagenesis libraries for antibody affinity maturation, using a cell-free solid-phase technique for annealing of single-strand mutagenic oligonucleotides.

11:45 Generation of Neutralising Antibodies against Tenascin-C: Targeting Early Changes in the Synovial Microenvironment as a New Class of Immunotherapy?

Slavny_PeterPeter Slavny, PhD, Project Leader, IONTAS Ltd.

Tenascin-C is a matrix molecule that drives chronic inflammation in models of rheumatoid arthritis (RA) via activation of Toll-like receptor 4. Here, we will discuss the generation, optimization, and characterisation of neutralising antibodies, recognising the fibrinogen-like globe (FBG) of tenascin-C. These potentially constitute a new drug class that could offer early, disease-specific immune modulation in RA, without engendering global immune suppression.

12:15 Targeting Membrane Proteins Using Isogenica’s Synthetic VHH Libraries

Hermans_Guy_PGDGuy Hermans, PhD, CSO, Isogenica Ltd.

Isogenica’s llamdA™ library is a highly diverse, fully synthetic single domain VHH library. We will illustrate some of the unique benefits of VHH technology over conventional antibodies and demonstrate how the unbiased diversity and lack of tolerance enables rapid and resource efficient isolation of VHH to membrane proteins. Examples will include the use of the library in ‘whole cell’ panning projects, as well as in selections using purified membrane proteins complexes.

12:45 Luncheon Presentation I: Streamlining the Biologics Development Process with the ExpiCHO Expression System

Chao_Yan_LiuChao Yan Liu, Associate Director, Cell Biology of the Life Sciences Solutions Group, Thermo Fisher Scientific

The ExpiCHO™ transient expression system offers a turnkey solution for generating high-titer recombinant proteins for therapeutic drug development, reagent generation, as well as an alternative platform for proteins that express poorly in 293-based systems.  Here, we present data on the optimized expression of antibody and non-antibody proteins in the ExpiCHO Expression System as well as solutions for generating stable ExpiCHO cells lines for GMP manufacturing.

TWIST-Bioscience 13:15 Luncheon Presentation II: Synthetic DNA Technologies Enable Antibody Discovery and Optimization

Aaron Sato, PhD, CSO, Biopharma, Twist Bioscience

Utilizing its proprietary DNA writing technology to create oligo pools, genes, and synthetic libraries, Twist Pharma, a division of Twist Bioscience, provides the biotechnology industry with an end-to-end antibody discovery solution. This solution includes (1) a panel of high-diversity synthetic antibody libraries, (2) a proprietary human anti-GPCR antibody phage display library focused on this validated target class, and (3) a Twist Antibody Optimization (TAO) platform for antibody affinity and developability optimization.

13:45 Dessert Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)

Auditorium VII

14:15 Chairperson’s Remarks

Barbas_AnaAna Barbas, PhD, Coordinator, Bayer Satellite Laboratory at iBET, iBET and Bayer Portugal SA

14:20 Synthetic Antibody Discovery against Native Antigens by CRISPR/Cas9-Induced CDR Variability

Goncalves_JoaoJoão Gonçalves, PharmD, PhD, Tenured Associate Professor, Faculdade de Farmácia Universidade Lisboa; Group Leader/Principal Investigator, Research Institute for Medicines/Instituto de Investigação do Medicamento (iMed.ULisboa)

Despite the significant advances of antibodies as therapeutic agents, there is still much room for improvement concerning the discovery of these macromolecules. Here, we present a new synthetic cell-based strategy that takes advantage of eukaryotic cell biology to produce highly diverse antibody libraries, and simultaneously link them to a high-throughput selection mechanism, replicating B-cell diversification mechanisms. The interference of site-specific recognition by CRISPR/Cas9 with error-prone DNA repair mechanisms was explored for the generation of diversity, in a cell population containing a gene for a light chain antibody fragment. This targeted variability strategy can be integrated with an intracellular selection mechanism. We successfully obtained lead candidates against several therapeutic targets both as small-domain antibodies and fully human IgG.

14:50 From Nanobodies to Megabodies for Applications in Cryo-EM

Steyaert_JanJan Steyaert, PhD, Francqui Research Professor at the Vrije Universiteit Brussel (VUB); Director, VIB-VUB Center for Structural Biology, VIB

Nanobodies (Nbs) are highly popular and versatile tools for structural biology. Here we report the development of megabodies, whereby Nbs are rigidly grafted into selected protein scaffolds to increase their molecular weight while retaining the full antigen-binding specificity. The megabody design principles are applicable to other scaffolds without size limitations and expand cryo-EM analysis to proteins that are small and/or display preferential orientation in ice, two major factors that limit the resolution of reconstructed density maps.

15:20 Next Generation Platforms for Antibody Discovery

Bradbury_AndrewAndrew R.M. Bradbury, MB BS, PhD, CSO, Specifica, Inc.

Antibody display libraries have served as a rich source of therapeutic antibodies. However, antibody leads selected from display libraries usually require downstream affinity and developability optimization, extending lead development timelines and costs. Specifica has established a unique antibody discovery display platform based on natural antibody sequences in which subnanomolar antibodies, requiring minimal optimization, are routinely selected.

15:50 High Quality Antibodies for Therapeutic Applications

Molkenthin_Vera_PGDVera Molkenthin, PhD, Chief Scientist, AbCheck

AbCheck discovers and optimizes human antibodies for therapeutic applications leveraging several proprietary platforms, including in vitro and in vivo technologies. AbCheck delivers high-quality leads with subnanomolar affinities and good stabilities, which are compatible with different antibody designs, including bispecifics.

16:20 Refreshment Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)

17:00 Discovery of Potent Human Therapeutic Antibodies Using Phage and Yeast Display Technologies

Bouquin_ThomasThomas Bouquin, PhD, Head, Biologics Research France, Centre de Recherche de Vitry/Alfortville, Sanofi

This speech will present our strategy and process for the discovery of highly potent therapeutic human antibodies targeting soluble or membrane-anchored targets by means of phage display technologies, including naïve scFv, synthetic Fab, and immune libraries. Yeast display-based antibody engineering aiming at increasing antibody affinity or species cross-reactivity will also be presented.

17:30 Novel Strategies for the Generation of Yeast Surface Display and Phage Display Antibody Libraries

Zielonka_StefanStefan Zielonka, PhD, Associate Director, Protein Engineering & Antibody Technologies, Discovery Technologies, Global Research and Development, Merck Healthcare KGaA

Yeast Surface Display and Phage Display are promising platform technologies for antibody engineering. Still, generation of antibody libraries is a cumbersome process involving multiple steps. During this talk, a focused approach for the construction of antibody libraries using type IIs restriction enzymes will be presented. This method seems to be valid for the generation of diversities with adequate qualities.

18:00 Single-Cell Technologies for Interpreting Antibody Function on a Repertoire Scale

DeKosky_BrandonBrandon DeKosky, PhD, Assistant Professor, Department of Chemical Engineering, Department of Pharmaceutical Chemistry, Kansas Vaccine Institute, The University of Kansas

Recently developed technologies in paired heavy:light sequencing, native antibody library display, and computational analysis of NGS datasets have opened up new possibilities for discovering and annotating antibodies from large populations of single B cells. We will discuss the development and application of these technologies to pair native human antibody sequences with their functional targets and to identify new antibodies with desired functional properties.

18:30 Using Phage Display to Select soloMERs that Target Cryptic Epitopes

Barelle_CarolineCaroline Barelle, PhD, MBA, CEO, Elasmogen Ltd.

SoloMERs are small, incredibly robust, single-chain binding domains. Elasmogen has exploited phage display to isolate these domains both from immunized and large diverse synthetic libraries against multiple therapeutic targets. This talk will focus on the propensity of these domains to bind cryptic epitopes and the advantages gained from combining these into multi-functional and multi-valent formats.

19:00 End of Display of Biologics