Phage and Yeast Display of Antibodies and Proteins

» Keynote Session 

8:30 Chairperson’s Opening Remarks 

 Lutz Jermutus, Ph.D., Senior Director, Research & Development; Global Head, Technology, MedImmune




 

8:40 Centocor Antibody Discovery from pIX Phage Display to Cell Line Development 

 William R. Strohl, Ph.D., Vice President, Biologics Research, Biotechnology Center of Excellence, Centocor 

The pathway for antibody discovery at Centocor will be presented, with a focus on the stages that are key components of the development process and technologies that are available. These include a novel pIX human antibody library, and technologies available for optimization, isotype selection, developability, epitope mapping, high content functionality screening, and cell line development. 

9:10 Engineering Antibodies for Medical Differentiation 

 Davinder Gill, Ph.D., Vice President and Head, Global Biologics Technologies, Pfizer, Inc. 

The talk will cover key aspects of antibody safety and efficacy as they relate to medical differentiation. This includes new modes of action as well as use of novel modalities. The importance of clear patient benefit in an increasingly crowded biologics area will be discussed. 

9:40 Selection of Internalizing Phage Antibodies Using Tumor Cells and Yeast Displayed Tumor Antigens 

 James D. Marks, M.D., Ph.D., Professor, Anesthesia and Pharmaceutical Chemistry; Chief of Anesthesia, San Francisco General Hospital; Vice Chairman, Anesthesia and Perioperative Care, UCSF 

Antibodies that bind cancer cells and are internalized can be used for tumor targeted drug and nucleic acid delivery. We show that such antibodies to specific tumor antigens can be generated by first selecting phage antibody libraries on a tumor cell line expressing the target antigen followed by selection on yeast displaying the same antigen on their surface. Advantages of this approach and specific examples will be covered. 

11:10 In vitro Recombination and HTS Screening Strategies for Potency, Selectivity and Antibody Germlining 

 Wayne Coco, Ph.D., Vice President Global Biologics / Biologics Lead Optimization, Bayer HealthCare AG Global Drug Discovery 

The optimization of antibody leads is important to maximize potency, best exploit animal models, shorten timelines to clinic/market and minimize risk. The choice of diversity to include into in vitro recombination libraries will be discussed as will the potential to rapidly and simultaneously affinity mature, alter specificity, germline and sequence optimize. 

4:45 Problem Solving Breakout Sessions 

Concurrent Problem Solving Breakouts are interactive sessions hosted by a moderator to discuss a topic in depth. They are open to all attendees, sponsors, exhibitors, and speakers and provide a forum for discussing key issues and meeting potential partners. Please pick a topic of your choice and join in. 

TABLE 1: Trends and Opportunities in Antibody Discovery 

Moderator: Lutz Jermutus, Ph.D., Senior Director, Research & Development; Global Head, Technology, MedImmune 

• Why would you need more than phage display and hybridomas to create antibody leads?
• Which technologies speed up early antibody CMC?
• How many “good” antibody targets are out there?
• How can we drug GPCRs, ion channel and other membrane proteins effectively using monoclonal antibodies? 

TABLE 2: Overcoming Limits Through Better Understanding 

Moderator: Nathalie Scholler, M.D., Ph.D., Assistant Professor, Obstetrics/Gynecology, University of Pennsylvania 

• Growth bias: phage vs. yeast display libraries
• Affinity vs. avidity: can too much display be not so wonderful?
• What controls for subtractive screening of complex samples? 

TABLE 3: Combining Phage and Ribosome Display 

Moderator: Maria A.T. Groves, Ph.D., Senior Scientist, Lead Generation, MedImmune 

• What are the key strengths of the phage and the ribosome display technologies for antibody generation?
• How can we apply phage and ribosome display to maximum effect when generating antibody therapeutics? 

TABLE 4: Next Generation Sequencing: Applications and Pitfalls 

Co-Moderators: Andrew M. Bradbury, M.B., B.S., Ph.D., Staff Scientist, and Chris Detter, Ph.D., Group Leader, Genome Science, Bioscience Division, Los Alamos National Laboratory 

• Errors in deep sequencing and their impact on studying the intrinsic variation of immune molecules
• Will we finally be able to sequence a full single chain Fv gene (~800bp)?
• Best deep sequencing platforms for the analysis of library selections 

TABLE 5: Next Generation Antibody Discovery 

Moderator: George Georgiou, Ph.D., Cockrell Endowed Chair Professor, Chemical & Biomedical Engineering and Molecular Genetics & Microbiology, University of Texas, Austin 

• What are the key technical issues in antibody repertoire sequencing and analysis?
• What can be learned from V gene repertoires?
• Which B cell subpopulations encode the most useful antibodies?
• How does antibody discovery via repertoire mining compare to other technologies for antibody isolation? 

TABLE 6: Internalizing Phage Antibodies 

Moderator: James D. Marks, M.D., Ph.D., Professor, Anesthesia and Pharmaceutical Chemistry; Chief of Anesthesia, San Francisco General Hospital; Vice Chairman, Anesthesia and Perioperative Care, UCSF 

TABLE 7: Considerations for Effective Phage Library Selection and Screening  

Moderator: Kristin Rookey, Principal Scientist, Dyax 

• How do you select for specificity?
• How do you drive for high affinity?
• How do you get to function faster?
• What screening methods are out there?
• How do you select and screen on cells?