- 生物制剂表现 -
The tools for creating novel biologics have resulted in a broad array of constructs with new modes of action and improved efficacy that are advancing to the clinic. The Fifth Annual Display of Biologics track showcases innovation in discovery, design and engineering of biologics through molecular evolution using phage, yeast and other display methodologies. Insights will be shared on using big data strategies and informatic analysis of next-generation sequencing outputs to improve library design and optimize drug molecules with greater potency, specificity, modes of action and activity than previously achievable.
Day 1 | Day 2
MONDAY 12 NOVEMBER | 09:00 - 12:00 | MORNING
Recommended Short Course*
SC2: Making Antibody Libraries in Phage and Yeast
Andrew R.M. Bradbury, MB BS, PhD, CSO, Specifica, Inc.
In this short course, students will learn about antibody basics, including structure, genetics and the generation of diversity, as well as the creation of naive antibody libraries in the phage and yeast display formats. This will include a description of phage and yeast display technologies, the creation of naïve libraries from natural and synthetic sources. The seminar will be fully interactive with students provided ample opportunities to discuss technology with instructors.
*Separate registration required.
MONDAY 12 NOVEMBER
12:00 Conference Registration
NOVEL TOOLS FOR TARGET DISCOVERY
13:30 Organizer’s Welcome
Christina Lingham, Executive Director, Conferences and Fellow, Cambridge Healthtech Institute
13:35 Chairperson’s Opening Remarks
Ana Barbas, PhD, Coordinator, Bayer Satellite Laboratory at iBET, iBET and Bayer Portugal SA
13:45 Yeast Surface Display Platform for Rapid Discovery of Conformationally Selective Nanobodies
Andrew C. Kruse, PhD, Associate Professor, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
G protein-coupled receptors (GPCRs) are the largest single class of transmembrane receptors in humans, and include important drug targets for the treatment of a broad range of diseases. We developed a synthetic VHH antibody fragment library displayed on yeast, which allows rapid and efficient isolation of antibody fragments that can bind and modulate GPCR signaling. These are powerful tools to investigate GPCR structure, function, and biology. Similar principles can be applied to identify conventional antibodies that can serve as surrogate agonists, antagonists, and allosteric modulators of GPCR signaling.
14:15 Back to the Future: Bacteriophages as Promising Therapeutic Tools
Pilar Domingo-Calap, PhD, Postdoctoral Researcher, Department of Genetics, Institute for Integrative Systems Biology, University of Valencia
The recent emergence of multi-drug-resistant bacteria needs for alternative therapies, and bacteriophages are potential antibacterial agents. In addition, bacteriophages can be used as promising tools in engineering genetics, mainly thanks to phage display. Drug discovery, vaccine development, antibody engineering, epitope mapping, gene/drug delivery or enzyme technology are examples of the potential use of phages in clinics. Thus, phages can be used in prevention, diagnosis and as treatment of specific diseases.
14:45 Phage Display as a Tool for Bispecific Antibody Generation
Andrew Nixon, PhD, Vice President, Biotherapeutics Molecule Discovery, Boehringer Ingelheim Pharmaceuticals, Inc.
Bispecific antibodies have become an important class of antibody drugs with application in a variety of therapeutic areas. Here, we will discuss identification of a pair of serine protease inhibitors from a phage display library, in vitro and in vivo characterization and creation of a dual inhibitory bispecific antibody. Finally, we will review alternate bispecific antibody formats, challenges and applications.
15:15 Further Advancement for Human Ab Discovery
Vera Molkenthin, PhD, Chief Scientist, AbCheck
AbCheck has developed Mass Humanization to generate humanized libraries. This approach utilizes batch cloning of CDR3 immune repertoires from immunized rabbits into selected human frameworks containing specifically diversified CDR1 and CDR2 regions. For selecting high affinity binders from the resulting, highly diverse library, AbCheck routinely applies Phage or Yeast Display under various conditions. In this talk, AbCheck will present new technological developments regarding its human antibody discovery and optimization platform.
15:45 Networking Refreshment Break
PLENARY KEYNOTE SESSION
16:15 Moderator’s Opening Remarks
Janine Schuurman, PhD, Corporate Vice President, Research & Innovation, Genmab BV
16:20 Bicycles and Bicycle Drug Conjugates
Sir Gregory Winter, PhD, FRS, Master, Trinity College and Co-Founder and Director, Bicycle Therapeutics
Bicycles® are a novel therapeutic class of constrained bicyclic peptides that combine antibody-like affinity and selectivity with small molecule-like tissue penetration, tunable exposure and chemical synthesis. They have potential in many indications, including oncology, where Bicycles’ unique properties have been used to develop Bicycle Drug Conjugates™ (BDCs), a novel toxin delivery platform which greatly improves toxin loading into tumour tissues. A BDC is expected to enter clinical trial in Q1 2018.
17:20 Paracrine Delivery: Therapeutic Biomolecules Produced in Situ
Andreas G. Plückthun, PhD, Professor and Director, Department of Biochemistry, University of Zürich
Cancer will have to be fought with cocktails of therapeutics acting locally, which may have to include therapeutic antibodies against receptors, checkpoint inhibitors, as well as cytokines to modify the tumor microenvironment. We have recently developed a technology of using non-replicative adenovirus carrying no viral genes, engineered to target desired cells and also to be shielded from the immune response, as a vehicle for simultaneous delivery of multiple genes of therapeutic proteins, produced and secreted by the infected cells.
18:20 Welcome Reception in the Exhibit Hall with Poster Viewing
19:30 End of Day
Day 1 | Day 2
TUESDAY 13 NOVEMBER
07:45 Registration and Morning Coffee
EMPOWERING NOVEL THERAPIES
08:30 Chairperson’s Remarks
Kerry Chester, PhD, Professor, Molecular Medicine, University College London Cancer Institute
08:35 Virus-Like Particle Display of HER2 Induces Potent Anti-Cancer Responses
Arianna Palladini, PhD, Department of Experimental Diagnostic and Specialty Medicine (DIMES), University of Bologna
Susan Thrane, MSc, PhD, Postdoc, Institute for Immunology and Microbiology, Centre for Medical Parasitology, Copenhagen University
Monoclonal antibody therapy improves management of HER2-driven mammary carcinoma, but its utility is limited. Active vaccination represents a promising alternative. Using a novel virus-like particle platform, we developed an active vaccine with a high-density display of HER2. Vaccine induced anti-HER2 autoantibodies were able to prevent mammary carcinoma onset in transgenic mice and inhibit HER2-positive tumor growth in wild-type mice. This vaccine represents a cost-effective treatment for HER2-positive cancer.
09:05 Anticalin Drug Candidates Selected against Therapeutic Targets with Innovative Formats and Modes of Action
Arne Skerra, PhD, Professor & Chair, Technical University of Munich
Anticalin proteins are an emerging class of clinical stage biopharmaceuticals with high potential as an alternative to antibodies. Anticalins can be selected using phage display and bacterial surface display techniques against a wide range of medically relevant targets, from small molecules to peptides and proteins. Their mode of action comprises growth factor antagonists, receptor agonists and small molecule scavengers/antidotes. Moreover, Anticalins allow molecular formatting as bi- and even multispecific fusion proteins, also in combination with antibodies that provide a second specificity.
09:35 Direct Functional Screening for Antibody-Drug Conjugates Using Transpo-mAb Mammalian Cell Display
Roger R. Beerli, PhD, CSO, NBE-Therapeutics AG
Transpo-mAb is a novel and highly efficient non-viral antibody discovery and engineering platform, allowing for the efficient display of full-length antibodies on the surface of B lymphocytes. Due to a built-in switch between surface and secreted expression, functional screening can be seamlessly integrated into the antibody discovery workflow. A case study showcasing the direct identification of fully human mAbs suitable as backbones of antibody-drug conjugates will be presented.
10:05 Problem-Solving Breakout Discussions
10:30 Coffee Break in the Exhibit Hall with Poster Viewing
NOVEL USES OF DISPLAY TECHNOLOGIES
David Lowe, PhD, Senior Director, R&D, Antibody Discovery and Protein Engineering, MedImmune Ltd.
11:15 Discovery of a Cryptic Peptide Binding Site on PCSK9 and Design of Antagonists
Yingnan Zhang, PhD, Senior Scientific Manager, Early Discovery Biochemistry, Genentech
PCSK9 is a negative regulator of hepatic LDLR. Discovery of small molecule therapeutics is hampered by the relatively flat EGF(A) binding site on PCSK9. We discovered that P’-helix of PCSK9 is flexible to reveal an N-terminal groove adjacent to EGF(A) binding site. Peptides accessing the groove were discovered from a phage displayed anchor-peptide-directed library and were further engineered into antagonists, which encroach on the EGF(A) binding site and inhibit LDLR binding.
11:45 Microfluidics and Genomics for Polyclonal and Monoclonal Antibody Drugs for Infectious Disease
David S. Johnson, PhD, Founder and CEO, GigaGen, Inc.
Human B cell repertoires encode a diversity of antibodies with high potential as therapeutics. Because of technical challenges, commercial groups do not typically make use of human B cell repertoires to identify candidates for antibody therapeutics. We have developed a suite of novel technologies to capture and express highly diverse, natively paired antibody libraries from human B cell repertoires. We are mining these libraries for efficacious monoclonal antibodies for infectious disease. We are also using the repertoires to manufacture recombinant hyperimmune polyclonal gammaglobulin drug candidates.
12:15 Presentation to be Announced
12:30 Screening Smarter to Derive Data Driven Decisions Faster
Sarah Payne, PhD, Product Manager, Marketing, TTP Labtech
There’s a smart way to increase the pace of therapeutic antibody and vaccine discovery. Derive data driven decisions faster with no-wash, cell, or bead-based immunoassay screening workflows that can be multiplexed to combine hit identification with selectivity, species cross-reactivity, viability, infectivity, or titer for accelerated decision making.
12:45 Luncheon Presentation I: The Journey to “the” Antibody: Accessing a Versatile Toolbox
Maria González-Pajuelo, PhD, CSO, FairJourney Biologics, S.A.
To maximize the possibility to select “the” antibody, at FJB we have taken antibody discovery to an unprecedented level by creating a versatile toolbox that allows the selection by phage display of antibody fragments of different species from large naïve and immune repertoires. Ultimately these fragments can be engineered and converted to mono- and bi-specific formats that are produced in CHO cells.
13:15 Luncheon Presentation II (Sponsorship Opportunity Available)
13:45 Dessert Break in the Exhibit Hall with Poster Viewing
COMPLEX SELECTIONS AND LIBRARIES
14:15 Chairperson’s Remarks
Gregory A. Weiss, PhD, Professor, Chemistry, Molecular Biology & Biochemistry, University of California, Irvine
14:20 KEYNOTE PRESENTATION: Single Cell Selections of Recombinant Antibodies Binding to Circulating Tumor Cells
Peter Kristensen, PhD, Associate Professor, Department of Chemistry and Bioscience, Aalborg University
Metastatic cancer is closely linked to circulating tumor cells. The mechanisms behind the dissemination of cancer through these metastatic seeds however remain incompletely understood. To reveal novel biomarkers, and gain a better understanding of the underlying mechanisms of cancer metastasis, we have used an advanced single cell selection on circulating tumor cells from patients diagnosed with metastatic colorectal cancer. In the presentation, the potential of single cell selection of recombinant antibodies will be discussed.
14:50 Dual Display: Phage Selection Driven by Co-Engagement of Two Targets
Oliver Hartley, PhD, Associate Professor, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva
This presentation will describe the design and preliminary evaluation of a new phage display approach enabling compatible pairs of antibody fragments to be co-selected based on co-engagement of their respective targets. Phagemids encoding a first scFv fused to phage g3p protein via a first leucine zipper are rescued in bacteria expressing a second scFv fused to a complementary leucine zipper, which is incorporated into phage during assembly.
15:20 Phage Display Selection of Chemically Cyclized Peptides for the Development of Therapeutics
Christian Heinis, PhD, Professor, Laboratory of Therapeutic Peptides and Proteins, Ecole Polytechnique Federal de Lausanne (EPFL)
My laboratory is engaged in the discovery and development of cyclic peptides for therapeutic application. A major focus is the generation of ligands based on bicyclic peptides by phage display. In my talk, I will present new chemical reactions that we have applied to generate structurally highly diverse cyclic peptide libraries, and I will show recent data on the therapeutic activity of bicyclic peptides in vivo.
15:50 Validation of Llamda, Isogenica’s Humanized Single Domain Antibody Library
Guy Hermans, PhD, CSO, Isogenica Ltd.
We have previously discussed the design and validation of llamdA, Isogenica’s fully synthetic camelid single domain antibody library. Here, we will disclose novel data on the design and validation of a humanized variant of the library. Examples will be provided on how this library, combined with our CIS Display enabled high throughput screening method, can generate high affinity lead panels in weeks rather than months.
16:20 Refreshment Break in the Exhibit Hall with Poster Viewing
17:00 KEYNOTE PRESENTATION: From Systems Biology to Systems Biologics
Sachdev Sidhu, PhD, Professor, Molecular Genetics, The Donnelly Centre, University of Toronto
We have established a platform to combine large-scale systems biology approaches with the discovery and development of new antibody drugs, and to develop efficient, systems-scale strategies to target intracellular signaling networks at the protein level with ubiquitin variants and other scaffolds. This efficient pipeline connects basic research to translational science in a new model for drug development, which we have termed “Systems Biologics”.
THERAPEUTIC APPROACHES TO AUTOIMMUNE DISEASE AND BEYOND
Ahuva Nissim, PhD, Reader, Molecular Targeting, Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London
17:30 Antibody Discovery at Bayer beyond Oncology
Rene Hoet, PhD, Head, Antibody Lead Discovery, Bayer AG
Traditionally, antibody therapeutic focus has been on oncology and autoimmune indications. More recently, the indication space has expanded to other therapeutic areas. In the presentation, case studies will be presented for lead discovery and optimization at Bayer of antibodies that are currently in clinical development for anti-thrombotic treatment (FXIa) and hemophilia (TIFP).
18:00 Discovering Antibodies against Challenging Epitopes and Challenging Antigens
Ruud de Wildt, PhD, Director, Head of Lead Discovery, Biopharm, GlaxoSmithKline
Raising antibodies to complex antigens or neo-epitopes is a considerable challenge. This talk will discuss the progress with the isolation of antibodies for a number of projects in the autoimmune disease area using GSK’s Antibody platforms. Innovative design and selection approaches will be discussed, including isolating antibodies against complex targets such as GPCRs and methods that allow the isolation of antibodies against antigens that are unstable or short-lived. Development of CAR T therapy for non-oncology applications will be discussed.
18:30 End of Display of Biologics