Antibodies Against Membrane Protein Targets - Part 2

 

( 膜タンパク質の標的に対応する抗体−パート2 )

Membrane-bound proteins are attractive drug targets for antibodies and other protein scaffolds, but for the field to advance, fundamental challenges in optimizing antigen quality and presentation, discovery methodologies, protein engineering and target identification must be resolved. This two-part meeting provides a forum in which discovery biologists and protein engineers can come together to discuss next-generation strategies and technologies that will allow antibody-based therapeutics directed against GPCR and ion channel targets to advance into the clinic and beyond. Part 2, Discovery, Characterization and GPCR/Ion Channel Updates, explores developments at the discovery and screening stages and offers focused sessions on each of these target classes.

RECOMMENDED PREMIUM PACKAGE:
Choose 2 Short Courses and 2 Conferences/Training Seminars
September 16 Pre-Conference Short Course: SC2: Targeting of Ion Channels with Monoclonal Antibodies
September 17-18 Conference: Antibodies Against Membrane Protein Targets – Part 1
September 18 Dinner Short Course: SC8: GPCR Structure-Based Drug Discovery
September 18-19 Conference: Antibodies Against Membrane Protein Targets – Part 2

Final Agenda

9月18日(水)

11:20 am Conference Registration Open


PLENARY KEYNOTE PROGRAM
Click here for full abstracts.

12:20 pm Event Chairperson’s Opening Remarks

An-Dinh Nguyen, Team Lead, Discovery on Target 2019, Cambridge Healthtech Institute

 

12:30 Plenary Keynote Introduction

Anjan Chakrabarti, Vice President, Discovery Chemistry, Syngene International Ltd

12:40 Base Editing: Chemistry on a Target Nucleotide in the Genome of Living Cells

David R. Liu, PhD, Howard Hughes Medical Institute Investigator, Professor of Chemistry & Chemical Biology, Harvard University

 

 

1:20 PROTACs: Past, Present, and Future

Craig M. Crews, PhD, Professor, Chemistry; Pharmacology; Molecular, Cellular & Developmental Biology; Yale University

 

 

2:00 Close of Plenary Keynote Program

2:00 Dessert Break in the Exhibit Hall with Poster Viewing

創薬戦略

2:45 Organizer's Welcome Remarks

2:50 Chairperson’s Opening Remarks

Brian Booth, PhD, Senior Scientist, Drug Discovery, Visterra

2:55 Therapeutic Antibody Affinity Maturation by Cell Surface Display: Closing the Gap

Kielczewska_AgnieszkaAgnieszka Kielczewska, Senior Scientist, Antibody Discovery, Amgen, Canada

AMGN12 antibody, derived from an in vivo immunization of the XenoMouse®, demonstrated single digit pM affinity to the human orthologue of the target protein, but a 200-fold weaker binding to the cyno orthologue. We applied a novel affinity maturation approach, based on combining non-hypothesis driven CDR-engineering with cell surface display, to “close” the affinity gap without compromising binding affinity to the human target. This led to identification of variants with affinity improvements and potency improvement in bioassays.

3:25 Lead Antibody Identification against Membrane Protein Targets Using Rabbit Single B Cell Cloning Technology

Takahashi_NoriyukiNoriyuki Takahashi, Unit Leader, Lead Identification Unit, Chugai Pharmabody Research, Singapore

Membrane proteins are attractive targets for drug discovery but antibody identification against membrane targets are challenging. Rabbit single B cell cloning technology is an immunization based powerful high throughput platform to identify lead antibodies. Our antibody identification strategy against membrane protein targets will be introduced.

3:55 Uncovering Novel Receptor Targets and Assessing Target Specificity against Human Membrane and Secreted Proteins

Kelly_AlexAlex Kelly, US Business Development Manager, Retrogenix Limited

Cell microarray screening of plasma membrane and tethered secreted proteins that are expressed in human cells enables rapid discovery of primary receptors as well as potential off-targets for a variety of biologics including: peptides, antibodies, proteins, CAR T and other cell therapies. Case studies will demonstrate the utility of the technology in identifying novel, druggable targets as well as in specificity screening to aid safety assessment and provide key data to support IND submissions.

4:25 Refreshment Break in the Exhibit Hall with Poster Viewing

GPCRに対応する治療薬の開発

5:00 Discovery and Optimization of Antibodies Targeting Ion Channels and G Protein-Coupled Receptors

Wilkinson_TrevorTrevor Wilkinson, PhD, Associate Director, Antibody Discovery and Protein Engineering, AstraZeneca BioPharmaceuticals Unit, United Kingdom

Multi-spanning membrane proteins such as GPCRs and ion channels are important drug target classes and are implicated in a broad range of diseases. There is significant interest in developing monoclonal antibodies directed against these target classes which exploit the unique properties of these therapeutics. This presentation will use case studies to address the challenges of isolating and optimizing antibodies against complex membrane proteins which have desired functional properties.

5:30 Development of Therapeutic Antibodies Targeting C5aR1

Booth_BrianBrian Booth, PhD, Senior Scientist, Drug Discovery, Visterra

The potent anaphylatoxin, C5a, promotes chemotaxis and activation of neutrophils, a key driver in inflammatory diseases such as ANCA-vasculitis. Blockade of the C5a-C5aR1 axis mitigates disease symptoms of ANCA-vasculitis animal models and in humans. An antibody targeting C5aR1 can provide improved specificity and pharmacokinetic properties and would be an ideal treatment modality for diseases involving complement pathway dysregulation. We detail the discovery of antibodies that antagonize the C5a receptor (C5aR1).

6:00 Discovery and Optimization of Fully Human CCR8 Antibodies with CCL1 Antagonistic Function using a Whole Cell Selection Platform

Robert Pejchal, Ph.D. Director, Antibody Discovery Adimab LLC

Whole cell selections extend discovery of IgGs to integral membrane proteins, such as GPCRs. A case study from initial binder identification to functional characterization of affinity-optimized antagonist leads against C-C chemokine receptor 8 (CCR8) will be presented, along with takeaways for leveraging multiple cell lines to effect the largest clonal frequency changes in NGS-based enrichment analysis of highly-diverse library selection outputs.

6:30 Dinner Short Course Registration
Click here for details on short courses offered.

9:30 Close of Day

9月19日(木)

7:00 am Registration Open

7:30 Interactive Breakfast Breakout Discussion Groups - View All Breakouts

Grab a cup of coffee and join a breakout discussion group. These are informal, moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic.

Structure-Based Antibody Discovery and Design

Moderator: Christopher Corbeil, PhD, Research Officer, Human Health Therapeutics, National Research Council Canada

  • De novo design of antibodies: Useful and feasible?
  • Computational predictions in real-life projects: Better integration needed?
  • Using computational tools to access difficult-to-target proteins
  • Structure-based antigen design

Opportunities in Antibody Discovery for Membrane Proteins

Moderator: Christyne Kane, PhD, Senior Scientist, Biologics Generation, AbbVie Bioresearch Center

  • In vivo vs. in vitro Approaches: The pros and cons
  • Antibody Databases: Requirements for the ideal database
  • IHC Tool Antibodies: Best practices for generation

Characterization of Antibodies Against Membrane Proteins

Moderator: Joseph Rucker, PhD, Vice President, Research and Development, Integral Molecular, Inc.

  • Affinity and Kinetics: Useful approaches for characterizing antibody binding
  • Epitopes: Different techniques for epitope mapping; binning versus mapping; why do epitopes matter?
  • Cell Function: Integrating functional assays into antibody discovery and development

Additional Breakouts to be Announced

8:30 Transition to Sessions

イオンチャネルに対応する治療薬の開発

8:40 Chairperson’s Remarks

Jen Pan, PhD, Director, Translational Neurobiology, Stanley Center at the Broad Institute

8:45 Targeting Kv1.3 with Biologics: Venom Peptides, Antibodies and Things in Between

Wulff_HeikeHeike Wulff, PhD, Associate Professor, Pharmacology, School of Medicine, University of California, Davis

The voltage-gated potassium channel Kv1.3 is expressed in T cells, B cells, microglia and macrophages and has long been pursued as a target for T-cell mediate autoimmune diseases. It has more recently also emerged as an attractive target for reducing neuroinflammation associated with stroke, Alzheimer’s and Parkinson’s disease. This talk will discuss targeting of Kv1.3 with venom peptides or conventional monoclonal antibodies and compare these approaches to so called “knotbodies”.

9:15 Controlling Membrane Proteins with Photopharmacology

Trauner_DirkDirk Trauner, PhD, Professor, Chemistry, New York University

Photopharmacology endeavors to control biological function with synthetic photoswitches that interact in various ways with their biological targets. I will discuss the advantages and disadvantages of photopharmacology and its potential applications in biology and medicine, in particular with respect to controlling cell proliferation, cell migration, and targeted protein degradation. I will also touch on the use of biological binders (nanobodies, etc.) for targeting GPCRs and ion channels with photopharmacology.

9:45 Modulating the Function of the P2X7 Ion Channel with Antibodies and Nanobodies

Koch-Nolte_FriedrichFriedrich Koch-Nolte, PhD, Professor, Laboratory of Molecular Immunology, University Medical Center Hamburg-Eppendorf, Germany

The P2X7 ion channel is expressed by immune cells as a sensor for nucleotides released from stressed cells. Blockade of P2X7 ameliorates disease in animal models of sterile inflammation. We have generated antibodies and nanobodies that antagonize or potentiate nucleotide-mediated gating of P2X7 with high specificity and efficacy. We can engineer these biologics to target specific immune cell subsets and to tune the duration of P2X7 antagonism in vivo.

10:15 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced

10:55 High Throughput, High Resolution Electrophysiology in the Era of Genetic Variations

Pan_JenJen Pan, PhD, Director, Translational Neurobiology, Stanley Center at the Broad Institute

Whole-exome sequencing has rapidly expanded the genetic variation that are identified in control subjects and in disorders. Here we propose a framework and workflow to dissect the impact of human genetic variations on ion channels in health and in sickness, and present two examples of data-driven approach to investigate the impact of human genetics on risk genes using high throughput and high-resolution electrophysiology.

11:25 Targeting KCa1.1 Channels for the Treatment of Rheumatoid Arthritis

Beeton_ChristineChristine Beeton, PhD, Associate Professor, Molecular Physiology and Biophysics, Baylor College of Medicine

Fibroblast-like synoviocytes (FLS) upregulate KCa1.1 (BK) channels and become highly invasive and erosive during rheumatoid arthritis (RA). Blocking KCa1.1 inhibits their invasiveness and attenuates disease severity in animal models of RA. Combining blockers of KCa1.1 to target FLS and of Kv1.3 channels to target effector-memory T lymphocytes is synergistic in animal models of RA.

11:55 GPCR Focused Antibody Libraries Modeled on Natural Binding Motifs and Patented GPCR Antibodies

Qiang Liu, PhD, Director, Antibody Engineering, Biopharma, Twist Bioscience

To enable the discovery of functional GPCR antibodies, we grafted a large number of GPCR-binding motifs into a focused antibody library. By incorporating these motifs into the antibody heavy chain CDR3, we developed our first generation GPCR library. Another approach mined the patented GPCR antibody sequences and used the sequence information to guide the design of another synthetic library. We demonstrate the utility of both libraries to discover potent functional antibodies against multiple GPCR targets.

12:25 pm Session Break

12:35 Luncheon Presentation: OmniChicken® and OmniClic™: Engineering Antibody Diversity in vivo Through Transgene Design

Bill Harriman, PhD, MBA, Vice President, Antibody Discovery Services, OmniAb, a Ligand technology

1:25 Refreshment Break in the Exhibit Hall with Poster Viewing

スクリーニングと特性評価

2:05 Chairperson’s Remarks

Mariana Lemos-Duarte, PhD, Postdoctoral Researcher, Icahn School of Medicine at Mount Sinai

2:10 Massive Antibody Discovery Used to Probe Structure-Function Relationships of an Essential Gram-Negative Bacteria Outer Membrane Protein

Rutherford_SteveSteven Rutherford, PhD, Scientist, Infectious Diseases, Genentech

A diverse library of monoclonal antibodies was used to probe the extracellular loops of an essential Escherichia coli outer membrane protein. Epitope binning, mapping, and site-directed mutagenesis suggest that dispensable loops shield functionally important epitopes from antibody interference. Our workflow enables structure-function studies in cellular environments, provides insight into an essential outer membrane protein, and presents a method to assess therapeutic potential of antibody targets.

2:40 Cell-Based Assays to Characterize Ligands for Chemokine Receptor CXCR4

Van_Loy_TomTom Van Loy, PhD, Senior Postdoctoral Scientist, Rega Institute, K.U. Leuven, Belgium

G protein-coupled receptors (GPCRs) form an important family of membrane proteins and the single largest class of therapeutic targets. In GPCR drug discovery in vitro cell-based assays are of key importance to characterize ligands (small molecules, biotherapeutics) that target this receptor class. We will exemplify this by discussing both label-free and label-based methodologies used to profile ligands targeting chemokine receptor CXCR4, as well as several other related GPCRs.

3:10 Integrated Discovery Approaches for Challenging Membrane Proteins

Blankenship_JohnJohn Blankenship, PhD, Senior Investigator and Group Leader, Antibody Discovery, Novartis

Traditional antibody discovery processes often fail to deliver functional antibodies against complex multi-pass membrane proteins. A case study will be presented using multiple approaches – immunization, antibody display technologies, and high throughput screening – to identify and refine specific, functional antibodies against a challenging target, enabling incorporation of these antibodies into next-generation antibody formats.

3:40 Development of High Throughput Functional Screening for the Characterization of an Active State-Sensitive Antibody to Protein Kinase C

Lemos_Duarte_MarianaMariana Lemos-Duarte, PhD, Postdoctoral Researcher, Icahn School of Medicine at Mount Sinai

We have developed a high-throughput functional screening to explore PKC activation in the context of opioid receptor signaling and desensitization. We generated antibodies to a PKC epitope that is revealed upon activation. This strategy allowed us to obtain rabbit monoclonal antibodies to activated PKC with high affinity and specificity. This talk will highlight a novel antibody-based strategy, with a novel yeast display approach to antibody development, CRISPR-Cas9 to validate it and high content microscopy to explore PKC signaling.

4:10 Close of Conference
Please click here to return to the agenda for Antibodies Against Membrane Protein Targets – Part 1

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