Cambridge Healthtech Institute’s 2nd Annual
Deep Sequencing and Single Cell Analysis for Antibody Discovery
Best Practices and Technologies for Applying Repertoire Analysis to the Discovery of Therapeutic Proteins
January 23-24, 2020
Part of the Protein Engineering & Development pipeline
The rapid adoption of deep sequencing and single B cell analysis has given discovery scientists an extraordinary view into human and animal immune repertoires that is now informing all aspects of biopharmaceutical R&D. This dynamic field is bringing
together the disciplines of immunology, structural and computational biology, informatics, and microfluidics to offer previously unimaginable perspectives that will drive discovery of the next generation of biologic drugs. PepTalk’s 2nd Annual Deep
Sequencing and Single Cell Analysis for Antibody Discovery conference explores new science and technology in this field and how these advanced capabilities are being implemented and integrated with platforms, workflows, and traditional discovery methods.
Final Agenda
THURSDAY, JANUARY 23
7:45 am Registration (Sapphire West Foyer) and Morning Coffee (Sapphire West & Aqua West Foyer)
8:10 Organizer’s Welcome Remarks
Kent Simmons, Senior Conference Director, Cambridge Healthtech Institute
8:15 Chairperson’s Opening Remarks
Vu Truong, PhD, CSO & CEO, R&D, Aridis Pharmaceuticals, Inc.
KEYNOTE PRESENTATION
8:20 Deep Genetic Analysis of Human Antibody Repertoires
Bryan Briney, PhD, Assistant Professor, Immunology and Microbiology, The Scripps Research Institute
Exceptionally deep genetic analysis of antibody repertoires has revolutionized our understanding of humoral responses to infection and immunization. Emerging high-throughput single cell analysis techniques now allows us to link repertoire genetics
with cell phenotype, allowing us to study the development and maturation of the antibody repertoire at a scale and depth that has not previously been possible.
9:00 Discovery 2.0: Creating (Almost) Unlimited Diversity Using a Novel Nano-Scale B Cell Culturing System and a High-Throughput Platform for Bispecific Antibody and
Format Combinations
Elke Glasmacher, PhD, Head, Immune and Cell Biology, Roche, Germany
The applications of standard therapeutic antibodies created with conventional lead generation processes have reached their limitations. Rare epitopes or bispecific combinations in different formats that can find broader applications in various
disease areas are urgently needed. We generate maximal diversity to identify truly next-generation biologics using novel high-throughput techniques, including a nano-scale single cell imaging and selection technology and a combinatorial platform
to rapidly generate bispecific antibodies in differing formats.
9:30 How to Find What is Rare: Natural Immunity and Antibodies Targeting Complex Membrane Proteins
Marta Szabat, PhD, Project Leader, Abcellera
Antibodies offer significant selectivity advantages over small molecules to target complex membrane proteins. Yet, few have made it to clinic, primarily due to discovery challenges. Over the years, AbCellera has successfully completed several
antibody discovery programs targeting GPCRs and ion channels. We will share lessons and insights that were instrumental to those successes, centred on deep screening and a suite of cutting-edge technologies that includes intelligent antigen
formats, strategic immunizations, machine learning, and data visualization.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
11:00 Deep Sequencing Analysis of Phage Selection Outputs: Leaving Conventional Screening Behind
Stefan Ewert, PhD, Senior Investigator, Novartis Pharma AG, Switzerland
We will show adaptations to library design and panning strategies exploiting the full potential of deep sequencing analysis of phage selection output pools to identify specific and high affine antibodies without conventional screening.
11:30 Advancing Cancer Immunotherapy One Cell at a Time
Navin Varadarajan, PhD, Associate Professor, Chemical and Biomolecular Engineering, University of Houston
The engineering of genetically modified immune cells has enabled unique challenges in the design and manufacture of these products. I will describe single-cell technology platforms and molecular engineering approaches that we have developed to
identify the potency of immune cells, and how these are being implemented to improve the efficacy of cancer immunotherapy.
12:00 pm Accelerate Your Drug Discovery with Nicoya’s Alto: The World's First Digital, High-Throughput, Benchtop SPR System
Ryan Denomme, CEO, Co-Founder, Nicoya
Nicoya believes in empowering scientists. We know how important SPR data is for your next big discovery. That’s why we are awarding one accomplished scientist a New Product Grant for a free Alto SPR system. Come by to learn about the world’s
first fully automated, high-throughput, benchtop SPR system. Enter to win at https://alto.nicoyalife.com/peptalk2020/
- limited spots available! You must be present to win. The future of drug discovery is digital. Join the movement.
12:30 Session Break
12:40 LUNCHEON PRESENTATION: Screening Broad B Cell Diversity to Accelerate Therapeutic Antibody Lead Candidate Selection Using the Beacon Platform
Anupam Singhal, PhD, Technology Development, Marketing, Berkeley Lights, Inc.
Antibody discovery against difficult targets is hampered by the lack of available technologies for functional screening of B cell repertoires. The Berkeley Lights’ BeaconTM platform enables users to generate large, genetically-diverse
hit panels by screening multiple B cell compartments. Lead candidate down-selection is performed in 1 day by performing functional characterization during primary screening. Case studies will highlight how Beacon users are
dramatically accelerating development of next-generation antibody therapeutics.
1:10 Ice Cream Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
2:15 Chairperson’s Remarks
Stefan Ewert, PhD, Senior Investigator, Novartis Pharma AG, Switzerland
2:20 Combining Single Cell TCR Sequencing and Transcriptomics to Discover Tumor-Specific T Cells by Unsupervised Learning
Alexander Yermanos, Researcher, Biosystems Science and Engineering, ETH Zurich, Switzerland
Identifying tumor-reactive T cells from cancer patients would be highly valuable in promoting TCR-based cell therapies. Recent advancements in single cell sequencing (scSeq) technologies have increased the resolution to which we can profile
tumor-infiltrating lymphocytes. We thereby performed scSeq of both TCR repertoires and whole transcriptomes of ~9,000 tumor-infiltrating T cells arising from a patient with lung carcinoma. We employed unsupervised learning to identify
tumor-specific T cells and tested their specificity to tumor cells.
2:50 NGS-Enabled Synthetic Ab Discovery
Jarrett Adams, PhD, Associate Director, Toronto Recombinant Antibody Center, Canada
Phage-displayed antibody repertoires are powerful resources for the discovery and optimization of therapeutic antibodies. By utilizing Illumina sequencing technologies, we are able to interrogate phage-Fab populations to fully map paratope
distributions and rapidly identify rare but functional antibodies with minimal screening. This approach has provided a simple means of minimizing epitope bias from antibody discovery campaigns, while enhancing our ability to target
antigens in context of cell.
3:20 Networking Refreshment Break (Sapphire West & Aqua West Foyer)
3:45 Long Read Next-Generation Sequencing and Machine Learning for Antibody Discovery
Andrew R.M. Bradbury, MB BS, PhD, CSO, Specifica, Inc.
Selection of potential antibody leads from display libraries is usually carried out by random colony picking. This approach is biased by dominant clones and explores rare clones inefficiently. We have developed an unsupervised machine-learning
approach to PacBio sequencing of selection outputs to maximally explore epitope space to generate highly diverse antibody panels against specific targets.
4:15 High-Throughput Functional Screening of Immune Repertoires
Bob Chen, PhD, Director, Engineering; Co-founder, xCella Biosciences
Here we present xPloration, an innovative drug discovery platform that enables high-throughput and high-content screening of millions of antibody-secreting cells. This image-based micropore array technology is compatible with a wide variety
of assay formats, including cell surface binding assays, reporter cell stimulation, and cross-reactivity screening. When combined with single cell sequencing at scale, this platform is enabling deep functional profiling of immune repertoires.
4:45 UPDATE: Speaker has cancelled. Delegates may attend parallel tracks. ANTAEUS: Next-Generation Antibody Discovery and Repertoire Analysis
Jimmy Gollihar, PhD, Research Scientist, Army Futures Command, Army Research Laboratory
The ANTAEUS (Antibody Accelerated Engineering by a Universal Selection) platform integrates three major technological innovations in order to enable unprecedented scale, ease and fidelity of functional antibody repertoire interrogation: 1)
Our rapid, novel antibody-antigen interaction reporting method, PRIMP; 2) Next-generation barcoding for massively parallel NGS-based data analysis; and 3) A humanized yeast strain capable of reliable population-wide display of native Fab
fragments.
5:15 Close of Day
FRIDAY, JANUARY 24
8:00 am Registration (Sapphire West Foyer)
8:00 BuzZ Sessions with Continental
Breakfast
Protein therapeutics is a fast-growing global market. As the science improves, so does the complexity of the R&D organization. Ensuring product quality plus speed to market requires insights from stakeholders working
across the stages of protein science R&D. Join experts representing this PepTalk pipeline, peers, and colleagues for an interactive roundtable discussion. Topics include highlights from the week’s presentations,
new technologies and strategies, challenges, and future trends.
Click here for more details
9:00 Chairperson’s Remarks
Aude Segaliny, PhD, Group Leader, Assay Biology & Scientific Liaison, Amberstone Biosciences
9:05 High-Throughput Interrogation of Cancer Patient Repertoires for Discovery of Anti-Tumor Antibodies
Sean Carroll, PhD, Associate Director, Molecular Biology, Atreca
Patient antibody repertoires can be the source of potent anti-tumor antibodies that bind novel targets. ATRC-101 (Ph1 ETA early 2020) is a recent example of a patient-derived antibody that exhibits potent anti-cancer activity
in pre-clinical models. In this presentation, we will demonstrate advances in display-based interrogation of cancer patient antibody repertoires in a target-agnostic manner for the high-throughput discovery of anti-tumor
antibodies.
9:35 B Cell Repertoire Screening Using Nanoculture Arrays and Rapid Production of mAb Using Cell Fusion
Vu Truong, PhD, CSO & CEO, R&D, Aridis Pharmaceuticals, Inc.
We developed a nanoculture array that is able to comprehensively screen the B cell repertoire and assess mAb binding at single cell level, and also engineered a fusion partner cell line designed to immortalize the selected
B cell, effectively enabling mAb production without the need for a recombinant step.
10:05 Single-Cell Droplet Microfluidics for Discovery of Therapeutic Antibodies
Aude Segaliny, PhD, Group Leader, Assay Biology and Scientific Liaison, Amberstone Biosciences
Discovery of functional antibody leads for therapeutic targets remains challenging. Several bottlenecks of conventional methods prevent users to efficiently and rapidly screen for antibody function, such as screening time,
cost and inability to recover precious rare clones. Here, we present case studies to show the power of AmberFlowTM in overcoming those challenges, a cutting-edge microfluidic-based, single-cell platform technology used
for discovery of functional antibodies against immunotherapeutic targets.
10:35 Networking Coffee Break (Sapphire West & Aqua West Foyer)
11:00 Continuous Evolution of Affinity Reagents with an Orthogonal Replication System in Yeast
Alon Wellner, PhD, Postdoctoral Research, Biomedical Engineering, University of California, Irvine
We have engineered a system that enables continuous evolution of affinity reagents in yeast. The gene encoding the antibody is orthogonally replicated on a cytoplasmic linear plasmid that has an error rate 100,000x
higher than the nuclear DNA. We demonstrated conformationally selective nanobody affinity maturation against the AT1R GPCR. A library of computationally designed CDR3 variants was cloned into the system and allows
for discovery and affinity maturation of tight binders against a plethora of antigens without the need for ex vivo sequence diversification.
11:30 Bioinformatics Approaches for Analyzing Adaptive Immune Systems through Profiling of Antibody Repertoires with Immunosequencing Data
Yana Safonova, PhD, Postdoctoral Fellow, Computer Science and Engineering Department, University of California San Diego
Rapid development of DNA sequencing technologies opened new avenues for analyzing adaptive immune systems through deep interrogation of antibody repertoires. Recent immunoinformatics studies revealed poorly understood
properties of antibody immune response. In this talk, I will show how computational analysis of antibody repertoires can be used in estimating efficacy of vaccines and designing antibody drugs. We will also
discuss the future of immunoinformatics as a high-priority direction of personalized medicine.
12:00 pm Conference Wrap-Up
Samantha Phan, Consultant Biologist, Protein BioSciences, Eli Lilly and Company
12:30 Close of Conference