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


7:45 am Registration and Morning Coffee

Antibody Discovery Applications

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.


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

Glasmacher_ElkeElke Glasmacher, PhD, Head, Immunobiology, 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 Presentation to be Announced

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 Deep Sequencing Analysis of Phage Selection Outputs: Leaving Conventional Screening Behind

Ewert_StefanStefan 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

Varadarajan_NavinNavin 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 Sponsored Presentation (Opportunity Available)

12:30 Session Break

Berkeley_Lights_Stacked 12:40 LUNCHEON PRESENTATION: Talk Title to be Announced

Singhal_AnupamAnupam Singhal, PhD, Technology Development, Marketing, Berkeley Lights, Inc.

1:10 Ice Cream Break in the Exhibit Hall with Poster Viewing

Rapid Screening and Machine Learning

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

Yermanos_AlexAlexander 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

Adams_JarrettJarrett 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

3:45 Long Read Next-Generation Sequencing and Machine Learning for Antibody Discovery

Bradbury_AndrewAndrew 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

Kelly_RyanRyan Kelly, PhD, Research Scientist, 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 ANTAEUS: Next-Generation Antibody Discovery and Repertoire Analysis

Golihar_JimmyJimmy 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


8:00 am Registration

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.

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Next-Generation Applications

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

Carroll_SeanSean 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

Truong_VuVu 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

Segaliny_AudeAude 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

11:00 Continuous Evolution of Affinity Reagents with an Orthogonal Replication System in Yeast

Wellner_AlonAlon 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

Safonova_YanaYana 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

Phan_SamanthaSamantha Phan, Consultant Biologist, Protein BioSciences, Eli Lilly and Company 

12:30 Close of Conference

* The program is subject to change without notice, due to unforeseen reason.

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2020 Conferences & Training Seminars