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2014 Archived Content

Cambridge Healthtech Institute’s Inaugural
Enhancing Antibody Binding and Specificity
Emerging Science and New Technologies to Fine-Tune Antibody-Antigen Binding
January 13-14, 2014


As the industry expands its repertoire of antibody drug products into new therapeutic areas, product formats and protein constructs, the control of antibody/antigen targeting, binding and specificity will take on a new level of importance for researchers in this field. The first component of the new PepTalk Antibody Optimization and Development pipeline, Enhancing Antibody Binding and Specificity, will present innovative approaches to the modulation of binding activity, mechanism of action and difficult target challenges such as transmembrane proteins and intracellular penetration.

Day 1 | Day 2 | Download Engineering Brochure | Speaker Biographies  

 

SUNDAY, JANUARY 12

4:00-5:00 pm Short Course Registration

5:00-8:00 Dinner Short Courses (SC1-SC7) More Details >> 

 

4:00-8:00 Main Conference Registration

MONDAY, JANUARY 13

7:30 am Conference Registration and Morning Coffee

 

Library Design and Screening for Novel Specificities 

9:00 Chairperson’s Opening Remarks

Germaine Fuh, Ph.D., Senior Scientist, Antibody Engineering, Genentech, Inc.

 

Keynote Presentation

9:10 Selections for Challenging Targets

Jim WellsJim Wells, Ph.D., Professor, Pharmaceutical Chemistry and Cellular & Molecular Pharmacology, University of California, San Francisco

Protein display technologies are proven for selecting high affinity binding proteins. But many technological challenges remain for selecting enzymes and antibodies that can activate functions, or bind specific PTMs. I’ll present recent work to select conformationally selective antibodies that can activate caspases, new scaffolds for anti-peptide antibodies for PTMs, a yeast display format for selection of novel peptide ligases, and finally a new automation platform for large scale protein selections.


9:50 Identifying Antibodies with Novel Specificity

Caroline ColleyCaroline Colley, Ph.D., Senior Scientist, Antibody Discovery and Protein Engineering, MedImmune

This presentation outlines the benefits of antibodies with novel specificities as therapeutic drugs and how MedImmune identifies candidate antibody drugs with the desired specificity profiles. Case studies will be presented covering various aspects of antibody specificity; including the isolation of target specific, conformation specific, mechanism specific and species-specific antibodies.

10:20 Coffee Break

10:45 Polyspecific Antibodies: Prediction of Structure and Design of Function

David NannemannDavid Nannemann, Ph.D., Postdoctoral Scholar, Chemistry and Pharmacology, Vanderbilt University

The Rosetta Macromolecular Structure Prediction Suite contains algorithms for atomic detail structure prediction and design of antibody and protein therapeutics. Integration of limited experimental structural data into prediction methodologies enables atomic detail description of antigen:antibody interfaces. Multi-state design algorithms allow for the study of antibody polyspecificity and provide a framework for engineering of antibodies with enhanced binding and broad specificity.

11:15 Enhanced Selection of Cross-Reactive Neutralizing Antibodies

Dimiter S. DimitrovDimiter S. Dimitrov, Ph.D., Senior Investigator, Protein Interactions Group, National Cancer Institute, NIH

Methods for enhanced selection of cross-reactive neutralizing antibodies will be overviewed. Several methods developed in our group including sequential and competitive antigen panning will be discussed in more details. Examples of enhanced selection of cross-reactive antibodies against viral and cancer-related antigens will be presented.

11:45 Cell-Based Selections against Complex Targets

Eric V. ShustaEric V. Shusta, Ph.D., Professor, Chemical and Biological Engineering, University of Wisconsin-Madison

Plasma membrane-resident proteins represent key targets in biology and medicine. However, standard antibody engineering approaches have been largely optimized for applications where soluble antigens are available. To address the added challenges inherent to antibody engineering against membrane protein targets, we have recently developed several tools that are compatible with antibody identification, analysis and engineering using whole cells or cell lysates as sources of membrane protein antigen.

 Vaccinex small12:15 pm Antibody Library Display on a Mammalian Virus:  Combining the Advantages of Panning and Cell Sorting in One Technology 

Smith_ErnestErnest S. Smith, Ph.D., Senior Vice President, Research & Chief Scientific Officer, Vaccinex, Inc.

We have developed an antibody discovery platform that enables efficient mammalian cell based expression of a library of human antibodies in full length IgG format on the surface of vaccinia virus. Upon infection of mammalian cells the antibody is not only incorporated into newly produced virus, it is also displayed on the surface of the host cell. This technology allows us to combine the advantages of virus panning and cell sorting into one technology.

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

 

Specificity Engineering 

2:00 Chairperson’s Remarks

Randall BrezskiRandall Brezski, Ph.D., Senior Scientist, Janssen R&D

 

 

 

2:05 Engineering Ph-Selective Antibodies

Nathan ScottNathan Scott, Ph.D., Principal Scientist - Biotherapeutic Discovery & Engineering, Pfizer


 


 

 

2:35 Engineering Antibodies against the Müllerian Inhibiting Substance Type II Receptor – Overcoming Obstacles Associated with a Highly Conserved Target

Greg AdamsGreg Adams, Ph.D., Co-Leader, Developmental Therapeutics Program, Fox Chase Cancer Center

The most interesting functional targets are often highly conserved between species making them particularly difficult targets for antibody generation. We have overcome prior failures of phage and immunization approaches by employing novel knowledge-based design strategies including homology modeling of the interaction of Müllerian Inhibiting Substance with its highly conserved Type II Receptor to develop antibodies that bind to the hormone’s binding site.

3:05 Molecular Mechanism and Utility of Converting a Monospecific Antibody to a Dual-Specific Two-in-One Antibody

Germaine FuhGermaine Fuh, Ph.D., Senior Scientist, Antibody Engineering, Genentech, Inc.

Antigen binding site of antibodies is built to interact with infinite varieties of molecules with high affinity and exquisite one-to-one specificity. I will describe a strategy that can be generally applied to engineer dual antigen specificity to a monospecific antibody and our understanding of its molecular mechanism using structural and thermodynamic studies that highlight the amazing capacity of the antigen-binding site to multitask. A Two-in-One anti-EGFR/HER3 is currently in clinical phase II for cancer treatment.

3:35 Selected Oral Poster Presentation: Target Identification and Characterization of Antibodies by Pathogen-Specific Genome-Wide Protein Microarrays

Emmanuel Yaw Dotsey, Ph.D., Postdoctoral Fellow, Department of Medicine Division of Infectious Disease, University of California, Irvine

3:50 Refreshment Break

4:15 Optimizing Antigen Affinity, Selectivity, and Clearance for Improved Antibody Therapeutics

John DesjarlaisJohn Desjarlais, Ph.D., Vice President, Research, Xencor

 

 

 

4:45 Engineering the Binding Site of an Antibody Against N-glycolyl GM3: From Functional Mapping to Novel Anti-Ganglioside Specificities

Gertrudis RojasGertrudis Rojas, Ph.D., Group Leader (Protein Engineering), Systems Biology, Center of Molecular Immunology

A combinatorial phage display strategy, based on the screening of a large soft randomization library, followed by refined mutagenesis, allowed both a comprehensive exploration and directed evolution of the binding chemistry of the unique anti-tumor antibody 14F7 (highly specific against N-glycolyl GM3 ganglioside). Novel variants that cross-react with a second poorly immunogenic glycolipid tumor-associated antigen (N-acetyl GM3) were obtained, overcoming the classical immunological barriers.

5:15 SMART-Ig: Novel Recycling and Sweeping Antibody Technology

Shinya IshiiShinya Ishii, Ph.D., Research Scientist, Research Division, Chugai Pharmaceutical Co Ltd., Japan

SMART-Ig recycling and sweeping antibody is an emerging antibody engineering technologies to release antigens at endosomal pH for reducing membrane bound antigen-mediated antibody clearance and increasing antibody-mediated soluble antigen clearance in vivo. In this presentation, various lead identification approaches for pH dependent antigen binding antibody, and various engineering approaches for further enhancing soluble antigen clearance will be presented.

/uploadedImages/Conferences/Logos/N-S/ProteinSimple.gif5:45-7:00 Welcome Reception in the Exhibit Hall with Poster Viewing 

 

Day 1 | Day 2 | Download Engineering Brochure | Speaker Biographies