Cambridge Healthtech Institute’s Second Annual
Emerging Technologies for Antibody Discovery
Cutting-Edge Technologies to Enable the Discovery of Novel
Biotherapeutic Targets for Antibodies and Emerging Constructs
January 12-13, 2017 | Hilton San Diego Bayfront | San Diego, CA
As large pharma continues its integration of biologic drugs into its product portfolios and discovery operations, it is imperative that industry companies identify truly novel drug targets for unmet medical needs. The Emerging Technologies for Antibody
Discovery meeting offers a forum for showcasing the current state of the art for research methodologies that will support the discovery of next-generation biotherapeutics. The meeting explores the evolution of traditional library and display approaches,
along with emerging technologies with the potential to have significant near-term impacts on the ability of scientists to discover and develop unique, differentiated biologic drugs.
Sunday, January 8
4:00 - 5:30 Short Course Registration
5:00 - 8:00 Dinner Short Courses*
Recommended Course: (SC1) Production Challenges for Complex Biologics: Antibody-Drug Conjugates and Fusion Proteins
* Separate registration required
TUESDAY, JANUARY 10
5:30 - 5:45 Short Course Registration
5:45-8:45 Dinner Short Courses*
Recommended Course: (SC8) Next-Generation Sequencing of Antibody Libraries: Details on Experimental and Bioinformatic Methods - Detailed Agenda
* Separate registration required
THURSDAY, JANUARY 12
7:45 am Conference Registration and Morning Coffee
8:15 Chairperson’s Opening Remarks
Michael Hornsby, Ph.D., Researcher, UCSF Antibiome and Recombinant Antibody Network, Pharmaceutical Chemistry, University of California, San Francisco
Keynote Presentation
8:20 The Adaptive Immune Receptor Repertoire (AIRR) Community: Developing Consensus Approaches for the Analysis and Sharing of Antibody/B-cell and Antibody/T-cell Receptor Repertoire Data
Jamie Scott, Ph.D., Professor, Faculty of Health Sciences, Canada Research Chair in Molecular Immunity, Simon Fraser University
The Adaptive Immune Receptor Repertoire (AIRR) Community is a grass-roots organization that is developing and coordinating standards for and best practices in the use of NGS technologies to study antibody (Ab)/B-cell and T-cell receptor (TcR) repertoires.
AIRR sequencing has enormous promise for understanding the dynamics of the immune repertoire in vaccinology, infectious disease, autoimmunity, and cancer biology, but also poses substantial challenges. The presentation will detail the progress
of this Community to date and outline new initiatives for the coming year.
9:00 Plug-and-(Dis)play Mammalian Cells for Protein Expression and Engineering
Sai Reddy, Ph.D., Assistant Professor, Biosystems Science and Engineering, ETH Zurich
Here I will present a platform for rapid reprogramming of hybridoma antibody specificity by immunogenomic engineering. We used CRISPR-Cas9 to generate targeted double-stranded breaks in immunoglobulin loci. Multiplexed-targeting enabled deletion of
the native variable light chain and homology directed repair allowed replacement of the endogenous variable heavy chain with a fluorescent reporter protein, mRuby. New antibody genes were then introduced by using Cas9 to target mRuby and promote
replacement.
9:30 Optimized Antigen Expression and Automated Antibody-Phage Display Pipeline for the Generation of Antibody Reagents to Cancer Related Surface Proteins
Michael Hornsby, Ph.D., Researcher, UCSF Antibiome and Recombinant Antibody Network, Pharmaceutical Chemistry,
University of California, San Francisco
I will describe our target discovery pipeline for identifying surface proteome changes in oncogene transformed cell lines. Along with this, we have optimized an antigen expression and purification workflow that supports our robotic antibody development
pipeline. Validated antibody reagents developed here have potential use as basic research tools and biotherapeutics.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
11:00 WebPhage: An Informatics Platform to Facilitate Biotherapeutic Discovery and Engineering
Steve Comeau, Ph.D., Principal Scientist, Vaccinex
The discovery of protein-based drugs frequently hinges on the effective interrogation of libraries containing billions of members. Advances in automated liquid handling have simplified library screening, but tools to capture and process associated
experimental data have not advanced at the same rate. To address this and support antibody discovery and protein engineering initiatives, Shire has developed a scalable workflow system, WebPhage, the design and future of which will be discussed.
11:30 Integrating Best-in-Class in vitro and ex vivo Assays to Manage Immunogenicity Risk in Biologics
Jeremy Fry, D.Phil., Director, Sales, ProImmune
Immunogenicity is one of the most complex issues to address in drug design and development. I will provide an overview of the best tools to mitigate immunogenicity risk, including Mass Spectrometry antigen presentation assays, DC-T and T-cell
proliferation assays for biologic lead selection/optimization, HLA-peptide binding assays to characterize individual epitopes as well as undiluted whole blood cytokine storm assays.
12:00 pm Protein-Protein Docking with Sequential Coarse-Grained Minimization
Nels Thorsteinson, Scientific Services Manager, Biologics, Chemical Computing Group
Protein-protein docking is an important tool for predicting affinity, optimizing properties and exploring druggable sites. This work presents a novel protein docking method for predicting protein-protein binding. The output protein poses are
shown to produce high-quality structures. The applicability of the docking program to antibody optimization will also be discussed.
12:30 Session Break
12:45 Luncheon Presentation: Cutting Edge Capillary
Electrophoresis Technology for Protein Analysis
Scott Mack, Staff Development Scientist, ProteinSimple
Analysis of protein samples by cIEF and CE-SDS is critical in establishing protein’s identity, purity, and heterogeneity. Maurice system combines two capillary electrophoresis (CE) detection schemes into one fully automated instrument,
using a proprietary ready-to-use cartridge design, allowing cIEF or CE-SDS data to be generated in a snap. Complimenting Maurice’s streamline operation is a novel native fluorescence cIEF detection mode which increases sensitivity
over absorbance. Presentation will review analysis of protein samples using Maurice system.
1:15 Ice Cream Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Remarks
Gregory C. Ippolito, Ph.D., Research Assistant Professor, Molecular Biosciences, The University of Texas at Austin
2:05 T-Cell Antigen Profiling by Deep Sequencing
Govinda Sharma, Ph.D. Candidate, Michael Smith Genome Sciences Center, BC Cancer Agency
Deep sequencing can now reveal the mutational spectrum of evolving tumors and the clonal diversity of tumor associated T cells. However, linking the two remains difficult. A small minority of T cells in the tumor environment are tumor-reactive
and they recognize only a small minority of potential tumor neoantigens. New approaches for direct and indirect neoantigen discovery and validation that are relevant to this problem will be discussed.
2:35 Natively Paired B- and T-Cell Immune Repertoires and the Discovery of Potent Antibody Therapeutics
Sean Carroll, Ph.D., Scientist, Atreca
Immune Repertoire Capture (IRC™) technology generates full-length sequences of natively paired variable regions from B and T-cells. Using IRC™, we have assembled repertoires from patients and models across multiple indications.
Analyses of these repertoires has uncovered specific receptor clonal lineages, facilitated cross-subject/time-point comparisons, and identified sequences for further characterization. This is leading to new immunologic insights
and identification of potent antibodies in immuno-oncology, infectious disease, and autoimmune disease.
3:05 Functional Therapeutic Antibody Discovery for Challenging Targets by Single-B-Cell Screening in Nano-Droplets
Roshan Kumar, Group Leader, Cambridge Site, HiFiBiO, Inc.
CelliGO is a fully integrated and highly efficient antibody discovery process combining the power of droplet-based microfluidics and single-cell-specific next-generation sequencing. Our ability to interrogate millions of B-cells per
experiment and deeply mine the immune response enables the discovery of valuable antibodies to diverse epitopes including rare functional epitopes.
3:20 The Trianni Mouse: Best-In-Class Technology for Human Antibody Discovery
David Meininger, Ph.D., Chief Business Officer, Trianni, Inc.
The Trianni Mouse is the only human transgenic antibody discovery platform offering a complete heavy, kappa and lambda repertoire in a single organism. Sequences of the variable domain exons are human while genetic machinery including
extensively optimized promoters and enhancers are of mouse origin.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15 Speaker has cancelled. Session will begin at 4:45 Immunosequencing Enables Novel Therapeutics Discovery via Unprecedented High-Throughput TCR or BCR Chain Pairing
Catherine Sanders, Ph.D., Director, Scientific Liaisons, Adaptive Biotechnologies
Building on Adaptive Biotechnologies’ TCR/BCR single chain sequencing technology, Adaptive has validated its pairSEQ approach that combines proprietary multiplex PCR methodology with high-throughput sequencing. By leveraging the diversity of the TCR repertoire, pairSEQ identifies native TCRα and TCRβ sequence pairs at an unprecedented throughput. Adaptive is further extending this approach to enable the identification of BCR heavy and light chain pairs for a broad spectrum of novel therapeutic applications.
4:45 Applying Sequencing Technology Combinations for Human Serum mAb Discovery
Gregory C. Ippolito, Ph.D., Research Assistant Professor, Molecular Biosciences, The
University of Texas at Austin
The synergistic combination of IgG protein mass spectrometry and B-cell VH:VL NextGen sequencing enables the facile discovery and testing of antigen-specific recombinant monoclonal antibodies (mAbs) mined from human serum.
We have documented the selective enrichment of serum mAbs for high-affinity binding, broad neutralizing activity, and potent in vivo protection in three case studies to date (poliovirus,
influenza, HIV). These data plus extrapolation of the technique to immuno-oncology will be presented.
5:15 Simultaneous DNA Barcoding of Proteins, RNAs and Natively Paired Immune Receptors from Millions of Single Cells for Immunotherapy Discovery
Adrian Briggs, Head, Technology Development, Receptor Discovery, Juno Therapeutics, Inc.
TILs hold the key to understanding anti-cancer immune responses but remain challenging to study due to their vast ranges of phenotype, function and abundance. Our single cell sequencing-based method allows deep and unbiased
TIL profiling directly from tumor tissue, providing insights into TIL diversity across a wide range of disease and sample types, with widespread potential for basic and applied research into the patient immune response
to cancer and the dynamics of immunotherapy.
5:45 Close of Day
FRIDAY, JANUARY 13
8:00 am Conference Registration and Morning Coffee
8:30 Chairperson’s Remarks
John Wheeler, Principal Research Scientist, Janssen BioTherapeutics
8:35 EM by EM: High-Efficiency Epitope Mapping Using High-Throughput Electron Microscopy
Claudio Ciferri, Ph.D., Scientist, Structural Biology, Genentech
We have implemented a fast and robust platform to perform epitope mapping using high-throughput Electron Microscopy (EM) and single particle analysis. This technology serves as an important tool for antigen design, selection
of therapeutic targets, and vaccine development. Future efforts will focus on streamlining the preparation of mAb-antigen complexes for Cryo-EM analysis to improve the resolution and obtain greater insights into antigen-antibody
recognition.
9:05 Measuring Oncogene Signaling with ImmunoPET
Michael Evans, Ph.D., Assistant Professor, Radiology and Biomedical Imaging, University
of California, San Francisco
We have pioneered a workflow in which we apply “omics” technologies to interrogate the biology downstream of an oncogene of interest to identify cell surface antigens that are compatible with PET imaging, and
selectively regulated by the oncogene. We have developed the first translational imaging tools to measure the activity of oncogenes like the androgen receptor, MYC, mTORC1, and RAS with PET, and we have begun to validate
these imaging biomarkers in man.
9:35 Using NGS to Enhance Cell-Based Antibody Phage Panning
John Wheeler, Principal Research Scientist, Janssen
Several receptor targets cannot be made as soluble proteins and others are problematic for discovery of antibodies that bind to native protein conformations. Cell-based phage panning can identify antibodies to such targets,
but is inefficient, often producing low antibody diversity. We utilized next generation sequencing to improve the robustness of cell-based selections. We have thus identified large panels of diverse antibody sequences
to several difficult receptor targets.
10:05 Coffee Break with a Poster Pavilion
11:00 Ultra-High Throughput Screening of Soluble, Secreted mAbs against Intact Cancer Cells
Yongliang Fang, Researcher, Thayer School of Engineering, Dartmouth College
We have developed a high throughput screening platform for the discovery and engineering of secreted, soluble, full-length mAbs that bind membrane proteins on the surface of intact target cells. This technology couples
fluorescence-activated cell sorting (FACS) with hydrogel microdroplet (GMD) encapsulation, thereby linking phenotype and genotype in ultra-high throughput library screens. This GMD-FACS platform makes a valuable tool
for antibody discovery and optimization in both academic and industrial settings.
View Speaker Interview
11:30 Antibody Libraries Based on an Autonomous Human Variable Domain
Johan Nilvebrant, Ph.D., Researcher, Biotechnology and Protein Technology,
Royal Institute of Technology
We have constructed two highly diverse (>1E10) libraries based on an autonomous human variable heavy (VH) domain. This scaffold was generated by comprehensive mutational analysis of residues in the former light chain
interface to identify structurally compatible hydrophilic substitutions that promote autonomous behavior. The libraries have been used to select binders to all 14 human Eph receptors, and we use these to investigate
effects of blocking or activation of specific Eph receptor homo- or heterodimers.
12:00 pm IT’S A WRAP: PEPTALK 2017 CLOSING PLENARY PANEL DISCUSSION
1:15 Close of Conference