2014 Archived Content

Engineering Antibodies

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7:00 am Registration and Morning Coffee

Selection of Biologically Active Antibodies 

8:00 Chairperson’s Opening Remarks

GregAdamsGregory P. Adams, Ph.D., Co-Leader, Developmental Therapeutics Program, Fox Chase Cancer Center

8:10 Keynote Presentation:
Identifying Functional Antibodies by Direct Expression in Reporter Cells

JohnMcCaffertyJohn McCafferty, Ph.D., Founder and CEO, IONTAS Ltd, United Kingdom

Using “traditional” cell-based screening assays we have generated a number of human antibodies that block cell signaling. We now report a novel system for identifying blocking antibodies by introducing antibody gene populations into ES reporter cells. Exemplified using FGF4 signaling, individual antibody-expressing ES clones exhibiting changes in differentiation outcomes are identified using lineage-specific gene expression allowing isolation of clones that encode and express signal-modifying antibodies.

8:40 Screening Antibody Phage Libraries in Product Format

Partha Chowdhury, Ph.D., Principal Scientist, MedImmune

Despite being a powerful technology for antibody discovery, phage libraries are severely limited because they cannot be directly screened in a relevant product format which is typically IgG. This talk will focus on the development and validation of a new technology that enables batch conversion of scFvs from phage libraries and high throughput screening as IgGs.

9:10 Preclinical Development of T Cell Directed Bispecific DART® Candidates

Ezio BonviniEzio Bonvini, M.D., Senior Vice President, Research, MacroGenics, Inc.

Selection of DART clinical candidates proceeds from in vitro physicochemical and functional analyses to in vivo activity modeling and toxicological assessment. Challenges in this category of products include on-target and off-target effects as well as acute phenomena related to T cell activation and cytokine release. A strategy integrating in vitro and in vivo studies aimed at defining parameters for clinical translation is discussed.

9:40 The Use of Structure and Rosetta to Design Phage Libraries for Antibody Optimization

Will SomersWill Somers, Ph.D., Vice President, Global Biotherapeutic Technologies, Pfizer

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

Antibody Therapeutics for Neurodegeneration 

11:10 Pathogenic Protein Targets for Neurodegenerative Disease Immunotherapies

AnneMesserAnne Messer, Ph.D., Professor, Biomedical Sciences, University at Albany; Senior Scientist, Neural Stem Cell Institute

Proteostasis in neurons and other mature cells breaks down as a result of a range of degenerative disease triggers and aging. Engineered antibody fragments are ideal reagents for validating and manipulating target proteins that are known to misfold. This presentation will cover examples of this approach, mainly focused on Huntington’s and Parkinson’s diseases.

11:40 Passive Immunization of Anti-α-Synuclein Antibodies Attenuate Pathological Synuclein Aggregates and Improve Behavioral Deficits in a Transgenic Mouse Model

RobinBarbourRobin Barbour, Head, Antibody Generation, Research, Prothena Biosciences

Over 2 million patients suffer from Parkinson’s Disease (PD) in the US/Europe. At this time, there is no proven disease-modifying therapy for PD. PD patients shows abnormal intracellular inclusions called Lewy Bodies, composed of α-synculein, a protein that is also genetically linked to the disease. We will discuss the outcomes of passive anti-α-synuclein immunotherapy studies in a transgenic mouse model of synucleinopathy.

12:10 pm Proprietary and Unique Expression System for Versatile and Ubiquitous Transgene Expression

Fisch_IgorIgor Fisch, Ph.D., CEO & Chairman, Selexis SA

Based on proprietary epigenetic regulator elements and leveraging the SURE CHO-M Genome and Transcriptome, Selexis has developed a mammalian expression platform capable of robust transcription and of overcoming complex secretion bottlenecks.  This technology has an extensive history of generating high-level, stable expressing cell lines, including cell lines producing difficult-to-express proteins such as Fc:fusions and large multimeric proteins.  The extensive characterization of the CHO-M cell line supports comprehensive and effective transfer packages for manufacturing. 

Origen12:40 Luncheon Presentation I: Evaluate Diagnostic Antibody Specificity by Using High Density Protein Microarray Technology

Ma-DonghuiDonghui Ma, Ph.D., CSO, Immunology, OriGene

Sensitivity and specificity are the two key features for a good diagnostic antibody. High density protein microarray technology is the best technology platform for antibody specificity evaluation. Here we showcase a novel protein microarray technology to evaluate target specificity for a couple of commonly used IHC diagnostic antibodies. Our data suggested that cross-reactivity is one of the reasons to create off-target staining. We will also introduce UltraMAB, the Ultra-specific monoclonal antibodies for anatomic pathology application.

1:10 Luncheon Presentation II: Human Single Domain Antibodies from the Crescendo Mouse

Young_JoyveJoyce Young, Ph.D., Head, Transgenic Platforms, Crescendo Biologics Ltd.

VH single domains are the smallest, most robust antibody fragments with advantages for topical delivery, tissue and tumour penetration, engineering of multivalent products and simple manufacture. The Crescendo Mouse harnesses the benefits of in vivo maturation to generate heavy chain antibodies as a source of fully human VH. Data from multiple programmes will be used to illustrate its ability to rapidly generate a high diversity of potent leads with excellent biophysical properties.

1:40 Session Break

High-Throughput Antibody Selection and Engineering 

2:00 Chairperson’s Remarks

Partha Chowdhury, Ph.D., Principal Scientist, MedImmune

2:05 High-Throughput Epitope Discovery Using Biosensor Technology

YasminaAbdicheYasmina Abdiche, Ph.D., Research Fellow, Rinat-Pfizer

We evaluated label-free biosensors that process 96 unique interactions simultaneously and several hundred interactions per experiment. Since cross-blocking of two monoclonal antibodies is necessary but not sufficient for them to bind the same epitope, high-resolution epitope binning assays determined by HT experiments can yield exquisite epitope discrimination. We also demonstrate that an antibody’s epitope and functional activity are correlated.

2:35 A High-Throughput Microfluidic Platform for the Discovery of Monoclonal Antibodies

CarlHansenCarl Hansen, Ph.D., Associate Professor, Center for High-Throughput Biology, University of British Columbia, Canada

We are developing a single cell antibody discovery platform for the screening of up to 400,000 single cells per experiment, followed by RT-PCR and recombinant expression of selected mAbs.  By eliminating the need for cell culture, this approach may used to find antibodies from any species, including fully human antibodies form patients. Moreover, our microfluidic format supports robust and long-term cell culture, making it uniquely suited for single cell mAb selections using cell-based assays, including cell binding, signaling inhibition/activation, apoptosis and proliferation.

3:05 A Unified Framework for Computer-Aided Biologics Design

Christopher R. Corbeil, Ph.D., Research Scientist, Chemical Computing Group

Protein engineering plays a pivotal role in modulating the function, activity and physical properties of biologics. Representative strategies employed in protein engineering include rational protein design and directed evolution. In general, disparate work has been done in applying computer-aided biologics design (CABD) to protein engineering for the development of novel biological therapeutics. Here, we establish a unified framework of protein engineering tools and investigate its applicability to modulation of protein properties: affinity and stability.

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing 

4:20 Droplet Microfluidics to Isolate Antibody-Secreting Cells

JohnHeymanJohn Heyman, Ph.D., Research Associate, School of Engineering and Applied Sciences, Harvard University

Droplet-microfluidics methods are increasingly used for single-cell analysis. Mammalian cells are viable for several hours within 40 pL aqueous drops, which are formed and sorted at rates >500Hz. Cell-secreted molecules remain trapped in the droplets, and in-droplet sandwich-type assays can identify and select cells that secrete desired antibodies. Here we report use of these methods to isolate non-immortalized antibody-secreting cells.

4:50 New Directions in Discovery of Antibodies from Native Sources Using NGS

TadasPanavasTadas Panavas, Ph.D., Principal Scientist, Molecular Protein and Biosciences, Janssen

With the means of next-generation sequencing combined with selective antigen specific B cell sorting we develop methods to molecularly clone antigen-specific antibodies from native or immunized sources. This technology bypasses the hybridoma fusion step and accelerates the timeline for isolation of mAbs. We compared natural mAbs derived from single B cells with antibodies resulting from artificial pairing of vH and vL from NGS analysis.

5:20 Networking Reception in the Exhibit Hall with Poster Viewing

6:30 End of Day


Measures to Enhance Half-Life and Stability - Detailed Agenda 

*Separate registration required

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