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Antibody Engineering
Event Information
The Annual Forum of the Antibody Engineering Community
Conveying the Insights Needed to Pioneer Future Developments in Antibody Engineering and Immunotherapeutics
December 02 - 06, 2007 . Sheraton San Diego Hotel and Marina . San Diego, CA
Document Title
Alternate Language Options:
大会议程
Pre-Conference Workshop
Sunday, December 2, 2007
| PRE-CONFERENCE WORKSHOP | DAY ONE | DAY TWO | DAY THREE | DAY FOUR | |
| Control of the Antibody Response |
| 12:00 | Registration Opens |
| 1:30 | Announcements |
| 1:35 | Chairperson's Opening Remarks
Jamie K. Scott, M.D., Ph.D., Professor and Canada Research Chair in Molecular Immunity, Department of Molecular Biology & Biochemistry, Simon Fraser University, Canada |
| 1:45 | B Cell Tolerance Checkpoints in Healthy Humans and Patients with Autoimmune Diseases
Significant progress has been made over the last few years in uncovering the B cell tolerance mechanisms that control the development of autoreactive antibodies. Our group has developed an approach that allows the single cell analysis of human Ig gene repertoire and BCR reactivity. Several checkpoints against autoreactive B cells have been established in the bone marrow and peripheral blood of healthy humans. Recent studies demonstrate that some of the autoimmune disorders are associated with several alterations of B cell tolerance checkpoints with a higher number of autoreactive B cells present in circulation.
Sergey Yurasov, M.D., Assistant Professor of Clinical Investigation, The Rockefeller University |
| 2:15 | Antibody Responses in Systemic Lupus Erythematosus
Systemic Lupus Erythematosus (SLE) is the prototypic systemic autoimmune disease characterized by polyclonal B cell activation. In this condition, autoantibodies appear to arise in germinal centers by somatic hypermutation and peripheral selection of mutated autoantibody encoding B cells. Analysis of the precise nature of the B cell abnormalities, especially those in disease-associated plasma cells and memory cells, should provide a basis for rational B cell directed therapy of SLE.
Peter E. Lipsky, M.D., Chief, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health |
| 2:45 | Variation in Expressed Antibody Gene Sequences in Response to Chronic and Acute Infections and in Autoimmune Disease
Broadly-neutralizing (bNt) antibodies against HIV are rarely produced; most have long CDR-H3s suggesting a role in broad neutralization. It has been proposed that bNt MAbs are rare, because they must develop from autoimmune precursors bearing long CDR-H3s. We compiled a database of 450 human MAbs of known specificity associated with chronic infection, acute infection or autoimmune disease, and found that long CDR-H3s correlate in general with anti-protein Abs, and to a lesser extent with chronic antigen persistence.
Felix Breden, Ph.D., Professor, Department of Biological Sciences, Simon Fraser University, Canada |
| 3:15 | Networking Refreshment Break |
| 3:45 | B Cell Subsets and Control of Memory in Murine Antibody Responses
Recent studies in which B cell progenitors committed to develop into B-1 cells were sorted from B cell progenitors committed to develop into B-2 cells definitely distinguish the two lineages. In this presentation, I will review these and additional data distinguishing cells at corresponding stages of development in the two lineages, from the earliest committed B cell progenitors to mature B cells and their plasma cell progeny. Finally, I will focus on the rapid B-1 antibody responses that follow in vivo stimulation with LPS and other stimuli, and will consider the roles these antibodies play in regulating other immune responses.
Leonora Herzenberg, Ph.D., Professor, Stanford University School of Medicine |
| 4:15 | Long Term Antibody Responses to Vaccines and Viral Infections
Vaccines are one of the most cost-effective medical treatments in modern civilization. Vaccines work by generating immunological memory, and long-term antibody responses are the correlate of protection for all human vaccines for which a correlate of protection is known. Recently, several groups, including ours, have focused on understanding how long term antibody responses are generated in humans, how long those responses last, and how they are maintained.
Shane Crotty, Ph.D., Assistant Professor, Vaccine Discovery Division, La Jolla Institute for Allergy and Immunology (LIAI) |
| 4:45 | Complement C3d-Mediated Activation of the B cells via CR2/CD19
The complement protein, C3d, enhances immune responses to conjugated antigens. C3d stimulates antigen presentation by FDC and helps to maintain immunological B cell memory. On B cells, C3d interaction with CR2 collects molecules such as CD19 and TAPA. CD19 triggers a signaling cascade resulting in cell activation and proliferation. Simultaneous C3d-CR2-CD19 ligation and surface immunoglobulin (sIg) by an antigen activates two signaling pathways that cross-talk to activate B cells resulting in the secretion of antibody.
Ted M. Ross, Ph.D., Associate Professor, Center for Vaccine Research, University of Pittsburgh |
| 5:15 | Close of Workshop Session; Start of Antibody Society General Session
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Special Evening Presentation
The Antibody Society: General Session |
| 5:30-7:30 pm |
(Open to all registered delegates of Antibody Engineering and Antibody Therapeutics. Workshop registration is not required.)
The Antibody Society was formed in 2007 to further the interests of antibody engineering and antibody therapeutics in their broadest sense, as well as to ensure safe and thorough testing of antibody therapeutics. The Society encompasses this increasingly diverse field by supporting the resources that promote successful engineering of recombinant antibodies, single scaffold binders, and other facets of basic and applied research by those in academics and the private sector. The Society also seeks to provide a forum and voice for the thousands of people now working on all aspects of this global field.
By joining The Antibody Society, members will support the development of significant activities, including:
- To encourage participation at important meetings in our field
- To establish committees that will assess topics of urgency, often including open discussion within our community
- To develop guidelines that help to ensure the safety of antibody-related therapeutics, during preclinical and clinical testing, and beyond
- To work for development and acceptance of formats for the interoperability of data, databases, and computational resources underpinning this field
- To work for the support, maintenance, and improvement of other critical resources in this field
- To develop mechanisms that encourage the training and funding of students, postdocs, and others in this field.
For further information on how you and your organization can join the Society, please visit the Society website at: www.AntibodySociety.org
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Main Conference - Day One
Monday, December 3, 2007
| PRE-CONFERENCE WORKSHOP | DAY ONE | DAY TWO | DAY THREE | DAY FOUR | |
| 7:30 | Registration, Networking Coffee |
| 8:00 | Announcements |
| Session I: Engineering Hybrid and Fusion Protein Immunotherapeutics |
| 8:05 | Chairperson's Opening Remarks and Keynote Introduction
James S. Huston, Ph.D., Vice President & Senior Research Fellow, EMD Serono - Lexigen Research Center |
| | Keynote Presentation
|
| 8:15 | Engineering Improved Immunotoxins for Cancer Therapy
Recombinant immunotoxins are chimeric proteins in which the Fv portion of a cancer-specific antibody is fused to a modified toxin. BL22 (CAT-3888), which is composed of an anti-CD22 Fv fused to a 38 kDa portion of Pseudomonas exotoxin A, produces complete remissions in patients with drug resistant Hairy Cell Leukemia, but has much lower activity in other CD22 positive malignancies with lower CD22 expression. We used protein engineering and phage display to increase the affinity and activity of the immunotoxin so that it kills cells with low CD22 expression. Clinical trials with this new agent (CAT-8015) have been initiated.
Ira H. Pastan, M.D., Chief, Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health |
| 9:15 | Audience Questions |
| 9:30 | Networking Refreshment Break |
| 10:00 | Immunocytokine Engineering & Therapy
Early clinical trials suggest that IL-2 based immunocytokines are most effective in patients with minimal residual disease. In contrast, a novel IL-12 based immunocytokine has now been shown in the veterinary setting to have anti-tumor activity against even large tumors, despite limitations due to immunogenicity of the human protein. We are now testing the potential synergy of IL-12 and IL-2 as part of a single immunocytokine in the same setting.
Stephen D. Gillies, Ph.D., President, EMD Serono - Lexigen Research Center |
| 10:30 | Co-Targeting ErbB2 and ErbB3 with a Bispecific scFv to Enhance Targeting Selectivity
We have developed a bispecific scFv, ALM, which co-targets the clinically relevant tumor associated antigens ErbB2 and ErbB3. ALM selectivity targets ErbB2/ErbB3 positive cancer cells both in vitro and in vivo and inhibits cell growth in vitro. The targeting selectivity of ALM, coupled with its therapeutic activity, suggests an approach for enhancing the efficacy of immunoconjugates for the treatment of cancer.
Matthew K. Robinson, Ph.D., Assistant Member, Department of Medical Oncology, Fox Chase Cancer Center |
| 11:00 | Single Chain Fab Fragments and Entirely Human Immunotoxins
By introduction of a polypeptide linker between Fd and the light chain, single chain Fab fragments (scFab) were generated. The impact of various linker designs and modifications of the constant region on both phage display efficiency and the yield of soluble antibody fragments in E.coli and Pichia pastoris was analyzed. Monovalent and divalent fragments (DiFabodies) as well as multimers were characterized.
Stefan Dübel, Ph.D., Director, Dept. of Biotechnology, Technical University of Braunschweig, Germany |
| 11:30 | Hybrid Protein Engineering
We have developed a novel engineering approach to produce heteromeric hybrid proteins directly from mammalian cells. The new platform confers desirable characteristics including control of multi-chain fusion protein design, simplicity of purification, high expression levels, and improved pharmacokinetics. This presentation describes the design and attributes of this platform technology.
Jonathan H. Davis, Ph.D., Senior Scientist, EMD Serono - Lexigen Research Center |
| 12:00 | Lunch on Your Own |
| | Technology Workshops
|
| 1:30 |  Case Study of DXL625 (CD20): A New Platform for Augmenting Antibody Therapeutics for Cancer
Potency is an important factor in determining the therapeutic efficacy for antibodies used to treat cancers. A novel enhancement strategy involves integrating self-binding peptides (DXL™). Anti-CD20 antibodies integrated with DXL™-peptide have higher binding avidity than the parent molecule. DXL™-anti-CD20 antibodies were also more potent inducers of apoptosis in cell based assays. Moreover, DXL™-anti-HER2 antibodies were significantly more potent than parent antibody in slowing tumor progression in a xenograft disease model. These studies suggest that DXL™-antibodies have greater potency than unconjugated forms and offer substantial improvement advancement in cancer therapeutics.
Thomas J. Kindt, Ph.D., Chief Scientific Officer, InNexus Biotechnology Inc.
and
Jeff Morhet, President, Chief Executive Officer and Chairman, InNexus Biotechnology Inc. |
| |  Therapeutic Antibody MOR103 for Treatment of Rheumatoid Arthritis
MOR103 is one of MorphoSys' own development programs and targets inflammatory diseases such as rheumatoid arthritis. By applying antibody maturation via CDR diversification the antibody has been optimized reaching a monovalent affinity in the low picomolar range. Along with the affinity maturation process, biological properties of the antibody improved immensely and epitope mapping demonstrated the generation of new sub-epitopes. MOR103 is currently in late preclinical development and results of lead generation, manufacturing and non-clinical pharmacology studies are presented.
Stefan Steidl, Ph.D., Project Team Leader, Research & Development, MorphoSys AG, Germany |
| 2:00 |  Balancing Power and Simplicity in Real-Time, Label-Free Characterization and Selection of Antibodies
This presentation highlights the usability of Attana's label-free and real-time molecular interaction analysis technology for selection and characterization of antibodies, with examples of how the technology can be implemented to increase the information about the interactions studied and the precision of the selection process. Another important feature is that detailed characterization of antibodies can be performed directly from crude culture media. This allows increased characterization quality, and reduces the time and cost for the characterization and selection process.
Björn Ingemarsson, Ph.D., Director, Product Management and Application Development, Attana, Sweden |
|  Strategies for Efficient Kinetic Characterization and Screening of Biomolecular Interactions Using BioLayer Interferometry
Abstract to come.
Speaker TBD, FortéBio |
| 2:30 | Announcements |
| Session II: Structural Aspects of Binding of Antibodies and Scaffolds to Peptides vs. Proteins |
| 2:35 | Chairperson's Opening Remarks
Andreas Plückthun, Ph.D., Professor of Biochemistry, Department of Biochemistry, University of Zürich, Switzerland |
| 2:45 | Structural Mechanisms for Evolving High Affinity Protein-Protein Interfaces
The affinity maturation process, whereby proteins evolve to bind their partners with improved affinity and specificity, offers a unique opportunity to examine the interplay of multiple biophysical factors in stabilizing protein-protein, including antigen-antibody, complexes. We are using directed evolution techniques to mimic affinity maturation in vitro. X-ray snapshots of affinity maturation pathways have been obtained that can be correlated with thermodynamic binding parameters to explain large (>1000-fold) increases in the affinity of protein-protein interactions.
Roy A. Mariuzza, Ph.D., Associate Professor, Center for Advanced Research in Biotechnology |
| 3:15 | Comparison of Antibodies Recognizing Proteins, Peptides and Haptens
Antibodies evolve to recognize any other molecules with exquisite specificity and high affinity. Such a feature has proven to be of great potential in molecular biology, clinical diagnostic research and therapeutic applications. This talk presents a comparison of antibodies that recognize proteins, peptides and haptens, showing their differences at the antigen-binding site topography, residues in contact with the antigen or specificity-determining residues as well as differential patterns of somatic mutations.
Juan Carlos Almagro, Ph.D., Principal Research Scientist, Centocor Research & Development, Inc. |
| 3:45 | Design of an Antibody Library Biased for Haptens
Large, naïve combinatorial antibody libraries have greatly facilitated our ability to develop specific human antibodies. However, certain features of such libraries are not always optimal for the development of specific binders against all targets. We have developed an approach in between large all-purpose libraries and rational design, as demonstrated with haptens as targets, that will facilitate identification of specific binders.
Mats Ohlin, Ph.D., Professor, Immunotechnology, Lund University, Sweden |
| 4:15 | Networking Refreshment Break |
| 4:45 | Maturing Antibodies in Escherichia coli through Hypermutations
Diversification of antibody sequences in human B lymphocytes occurs in two stages - V(D)J recombination and somatic hypermutations (SHM). While the former occurs prior to exposure of the cells to antigen, the latter process takes place in response to specific antigens. During the latter process, antibodies are actively mutated by the action of an enzyme called AID and antibodies with higher affinity to the antigen are selected. We are recreating this process in E. coli by expressing AID in this bacterium and using a variety of genetic and physical selection strategies.
Ashok S. Bhagwat, Ph.D., Professor of Chemistry, Wayne State University |
| 5:15 | A Human Protein Atlas using Antibody-Based Proteomics
We have used antibody-based proteomics to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in normal human tissues and different cancers. The Human Protein Atlas contains more than a million high-resolution images and is publicly available (www.proteinatlas.org). Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research, in particular for biomarker analysis in various patient cohorts.
Mathias Uhlen, Ph.D., Professor of Biotechnology, AlbaNova University Center, Royal Institute of Technology, Sweden |
| 5:45 | Antibodies and Armadillo Repeat Proteins as Peptide Binders
Peptides can be bound by antibodies in many different conformations, and their generation requires a new selection experiment for every peptide. In contrast, armadillo repeat proteins show a remarkably conserved binding mode even with unrelated peptides. Designed armadillo repeat proteins were thus developed as general scaffolds for peptide binding. Single specific repeats can be selected with a vision of combining them into new binding proteins without performing additional selections.
Fabio Parmeggiani, M.Sc., Researcher. Department of Biochemistry, University of Zürich, Switzerland |
| 6:15 | Networking Cocktail Reception; Opening of Poster and Exhibit Hall |
Main Conference - Day Two
Tuesday, December 4, 2007
| PRE-CONFERENCE WORKSHOP | DAY ONE | DAY TWO | DAY THREE | DAY FOUR | |
| 7:00 | Registration, Networking Coffee |
| 7:45 | Announcements |
| Session III: Single Scaffold Binders |
| 7:50 | Chairperson's Opening Remarks
Ian M. Tomlinson, Ph.D., Vice President, GSK-Domantis Group, United Kingdom |
| 8:00 | Taking Nanobodies® from Platform to Pipeline
Nanobodies are antibody-derived therapeutic proteins based on naturally occurring heavy-chain antibodies derived from camelids. Data is presented on the first Phase I clinical study with Nanobody ALX-0081, a bivalent humanized Nanobody targeting vWF that selectively blocks the adhesion of platelets to collagen. Further, the design and performance of a new, highly potent cytokine-receptor neutralizing Nanobody with long serum half-life is reported. These two examples of therapeutic Nanobodies demonstrate how the many benefits provided by this exciting protein discovery platform are translated into a pipeline of novel 'first-in-class' biopharmaceuticals.
Hennie Hoogenboom, Ph.D., Chief Scientific Officer, Ablynx NV, Belgium |
| 8:30 | Single Ig Variable Domains from Mice
We have developed a system to generate humanized llama and human VH domain heavy chain only complexes by introducing human heavy chain immunoglobulin loci that lack a CH1 domain in transgenic mice. These loci function like normal immunoglobulin loci and result in circulating transgene derived immunoglobulins. In a further development, we have generated tetravalent monospecific or tetravalent bi-specific heavy chain only antibodies.
Frank Grosveld, Ph.D., Chairman, Department of Cell Biology, Erasmus University, The Netherlands |
| 9:00 | Fully Human Domain Antibodies as Drugs
With the first dAbs now in the clinic and a broad pipeline of additional late stage preclinical assets following close behind, this talk reviews the latest preclinical and clinical data for the four major classes of dAb based drugs: monomeric dAbs to cell surface receptors, pulmonary delivered dAbs, AlbudAb fusions and Dual Targeting dAbs. Each class offers a series of unique advantages compared to conventional mAb based therapies and allows for novel drugs to be developed to well-validated targets.
Ian M. Tomlinson, Ph.D., Vice President, GSK-Domantis Group, United Kingdom |
| 9:30 | Networking Refreshment Break, Exhibit and Poster Viewing |
| 10:15 | DARPins in Cancer
Designed Ankyrin Repeat Proteins (DARPins) have been evaluated as targeting reagents in tumor models, some with affinities in the picomolar range. Their outstanding biophysical properties allow different molecular formats to be implemented easily. The interplay of format, affinity, internalization and in vivo targeting has been investigated and is discussed.
Andreas Plückthun, Ph.D., Professor of Biochemistry, Department of Biochemistry, University of Zürich, Switzerland |
| 10:45 | Adnectins: An Emerging Class of Protein Therapeutics
Adnectins are a new protein drug class being developed exclusively by Adnexus Therapeutics. Derived from a small domain of human fibronectin, it has been demonstrated that these proteins can be engineered to effectively hit multiple therapeutic targets using PROfusion, Adnexus' proprietary protein design engine. CT-322 is an inhibitor of VEGFR-2, and is the first Adnectin in clinical trials. CT-322 Phase I clinical data demonstrates the potential of Adnectins as a viable new product class to address important unmet medical needs.
Ray Camphausen, Ph.D., Vice President, Discovery, Adnexus Therapeutics, Inc. |
| 11:15 | Engineering Ig Constant Domains for Antigen Binding
f-star's Modular Antibody Technology can be used to engineer additional specificities into antibodies without change of the natural antibody format. Thus it provides a source for next-generation antibodies and improved versions of conventional monoclonal antibodies. We have developed large phage display libraries of immunoglobulin domains randomized in non-CDR-loop positions. Selected immunoglobulin domains can be used as building blocks in any antibody format and will be applied to tune specificity, avidity, effector functions and pharmacokinetics of antibody-based therapeutics.
Florian Rueker, Sc.D., Chief Scientific Officer, f-star Biotechnology, Austria |
| 11:45 | Technology Workshops
|
|  Composite Human Antibodies - Combined Humanization, Deimmunization and Fully-Human Antibodies
In order to address some limitations of humanization and deimmunization technologies, our laboratory has switched to generating composite variable regions from multiple sequence segments derived from different human antibodies to construct novel variable regions that have a low potential for immunogenicity. Composite Human Antibodies combine elements of humanization, deimmunization and fully-human technologies resulting in substantially new therapeutic antibody variable regions designed for low immunogenicity. The talk includes data from several antibody programs, especially for oncology.
Frank J. Carr Ph.D., Director, Biologics Research, Antitope Ltd., United Kingdom |
|  Surface Plasmon Resonance Analysis of High-Density Antibody Microarrays
In the antibody discovery process, potentially useful antibodies are identified through primary screening including ELISA, and further characterized using low-throughput surface plasmon resonance (SPR) instrumentation. Presented is a novel SPR microarray analyzer, the ProteomicProcessor™, that can analyze high-density antibody microarrays, and can combine screening and kinetic characterization in one easy-to-use platform.
Ronald P. Dudek, Director, Business Development, Plexera Bioscience, LLC |
|  XOMA Development Paradigm - From Discovery to the Clinic with XOMA 052
Using function forward strategies, XOMA designs customized therapeutic mAb discovery programs tailored to the specific target biology and guided by the desired product profile. XOMA's Ab technology platform is comprised of eight commercial human Ab phage display libraries, hybridoma technology coupled with proprietary Human Engineering™ technology, antibody optimization technologies, and an integrated biologics product development infrastructure. XOMA 052, an ultra high affinity anti-IL-1兝程mAb, is presented to illustrate this approach from antibody discovery to clinical development.
Mary Haak-Frendscho, Ph.D., Vice President, Preclinical Research & Development, XOMA (US) LLC |
| 12:15 | Networking Luncheon, Exhibit and Poster Viewing |
| 1:45 | Technology Workshops
|
|  The Role of ADCC and CDC Enhancement Technology for Clinical Applications in the Development of Next-Generation Therapeutic Antibodies
A robust and stable method for enhancement of ADCC activity is BioWa's POTELLIGENT® Technology. POTELLIGENT uses a proprietary fucosyltransferase-knockout CHO cell line to produce antibodies with reduced fucose in their carbohydrate structures. POTELLIGENT dramatically enhances ADCC activity of an antibody in vitro and increases antibody potency and efficacy. BioWa also created a method for enhancement of CDC activity called COMPLEGENTTM technology. COMPLEGENT enhances CDC activity more than 10-fold by Fc chimerism between IgG1 and IgG3.
Masamichi Koike, Ph.D., President and Chief Executive Officer, BioWa, Inc.
Kenya Shitara, Ph.D., Director, Antibody Business Unit, Kyowa Hakko Kogyo Co., Ltd. |
|  MORAb-028 - A Human Anti-cancer IgM Monoclonal Antibody
MORAb-028 is a therapeutic human IgM that recognizes G-28, a cell surface glycolipid expressed in various tumors including melanomas. MORAb-028 was generated from a natural IgM isolated from a melanoma patient via Morphotek's Human MORPHODOMA® technology. This precursor regressed tumor when injected in human melanoma lesions. MORAb-028 can effectively kill human melanoma cells via a complement mechanism. Morphotek has initiated product development and manufacturing of MORAB-028 to support submission of an IND in early 2008.
Luigi Grasso, Ph.D., Senior Vice President, Research & Development, Morphotek Inc. |
| 2:15 | Announcements |
| Session IV: Selection and Screening |
| 2:20 | Chairperson's Opening Remarks
Andrew Bradbury, M.B. B.S., Ph.D., Research Scientist, Los Alamos National Laboratories |
| 2:30 | Monoclonal Antibody Classification Based on Epitope Binding Using Differential Antigen Disruption
A novel antigen-structure-based screening approach called differential antigen disruption (DAD) was developed. This method enables one to classify a large number of mAbs according to their epitopes in a robust and an inexpensive manner. This mAb classification information can provide invaluable insights aiding mAb screening. The presentation will focus on the development and applications of the DAD technology for VelocImmune® human therapeutic antibody programs in Regeneron.
Ergang Shi, Ph.D., Senior Scientist, Regeneron Pharmaceuticals |
| 3:00 | Yeast Antibody Display for the Profiling of Cell Surfaces
We have developed new methods that employ yeast surface display for the identification of plasma membrane-resident biomarkers. A nonimmune human antibody library displayed on the surface of yeast was used to interrogate the surface of brain endothelial cells yielding membrane protein-antibody pairs without a priori knowledge of the membrane protein or antibody identities. To date, 34 such antibody-membrane protein pairs have been identified. In addition, the identified antibodies are being used to clone the cognate membrane protein antigens by a novel yeast display-based immunoprecipitation method.
Eric V. Shusta, Ph.D., Assistant Professor, Chemical and Biological Engineering, University of Wisconsin-Madison |
| 3:30 | Serum Antibody Fingerprinting with Bacterial Display
Serum antibodies are important biomarkers and their amplification by the immune system enables diagnosis of a wide variety of diseases. We coupled bacterial display with quantitative screening to identify and evolve peptide epitopes that recognize a rare target antibody with high specificity in the presence of competing serum antibodies. Bacterial display provides an effective means to enhance the specificity of antibody detection reagents for improved disease diagnosis.
Patrick S. Daugherty, Ph.D., Associate Professor, Chemical Engineering, University of California, Santa Barbara |
| 4:00 | Networking Refreshment Break, Exhibit and Poster Viewing |
| 4:45 | Discovery, Engineering and Production of IgG Antibodies in Bacteria
We have developed a number of complementary technologies for the discovery and production of full-length IgG antibodies in E. coli. Antibody discovery capitalizes on Anchored Periplasmic Expression (APEx), a FACS-based method for the isolation of clones displaying proteins on the inner membrane of the bacterium. The selection of antibodies from libraries of different designs, the engineering of IgG effector functions and the preparative expression of bacterially-expressed antibodies is discussed.
George Georgiou, Ph.D., Cockrell Chair in Engineering, Departments of Chemical Engineering, Biomedical Engineering, and Molecular Genetics and Microbiology, University of Texas, Austin |
| 5:15 | Antibody/Antigen Screening by Protein Fragment Complementation Assay
Protein fragment complementation Assay (PCA) is a relatively new strategy developed to investigate protein-protein interactions in vitro and in vivo, with the potential to become a simple and straightforward method for large-scale selection strategies. We have developed a procedure based on the complementation of the TEM-1 b-lactamase enzyme. The method was applied for the high-throughput screening of antibody and antigen libraries in E. coli.
Daniele Sblattero, Ph.D., Associate Professor, Department of Medical Sciences, University of Eastern Piedmont, Italy |
| 5:45 | Title to be Determined
Andrew Bradbury, M.B. B.S., Ph.D., Research Scientist, Los Alamos National Laboratories |
| 6:15 | Exhibit and Poster Hall Networking |
Main Conference - Day Three
Wednesday, December 5, 2007
| PRE-CONFERENCE WORKSHOP | DAY ONE | DAY TWO | DAY THREE | DAY FOUR | |
| 7:30 | Registration, Networking Coffee |
| 8:00 | Announcements |
| Session V: Recent Advances in Antibody Technologies |
| 8:05 | Chairperson's Opening Remarks
Dennis R. Burton, Ph.D., Professor, Immunology Department, The Scripps Research Institute |
| 8:15 | CovX-bodies: from Concept to Clinic
Recently, my laboratory has developed a new class of immunotherapeutic agents termed Chemically Programmed Antibodies or CovX-bodies as prepared by CovX Inc. I will present studies concerning the superior in vivo activity bestowed upon small molecules and peptides by this approach and describe how CovX Inc. has now advanced these molecules into human clinical trials.
Carlos F. Barbas, III, Ph.D., Professor, Molecular Biology and Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute |
| 8:45 | Harnessing Somatic Hypermutation for Antibody Selection and Optimization
Somatic hypermutation (SHM) is the natural process of antibody maturation that creates high-affinity antibodies by introducing sequence variation at the IgV (variable) locus via targeted deamination of deoxycytidine (dC) to deoxyuridine (dU) residues by activation-induced cytidine deaminase. Anaptys has created a human monoclonal antibody platform based on SHM in order to optimize antibody target binding site and affinity parameters to meet specific design goals.
William J. Boyle, Ph.D., President and Chief Science Officer, Anaptys Biosciences, Inc. |
| 9:15 | Yeast and Phage Display of Libraries
The introduction of antibody display technologies has greatly advanced the pharmaceutical industry by making the discovery and optimization of antibodies routine. However, there are limitations when using existing display technologies and selection methods to discover novel antibodies. Presented here is a new library selection methodology utilizing both yeast display and phage display to select antibodies.
Diana Bowley, Ph.D., Staff Scientist, The Scripps Research Institute |
| 9:45 | Networking Refreshment Break, Exhibit and Poster Viewing |
| 10:30 | IgG Expression and Engineering in Yeast
Saccharomyces cerevisiae can be used as an expression host for the secretion of whole IgG antibodies. We have engineered a secretory leader peptide that enables secretion of 1-20 mg/L whole IgG in shake flask cultures, and these antibodies are useful for immunofluorescent cell labeling, Western blots, and soluble immunoassays. This yeast expression system is a rapid means of obtaining useful quantities of IgG for reagent and preclinical purposes.
K. Dane Wittrup, Ph.D., J.R. Mares Professor, Chemical Engineering Department and Division of Biological Engineering, Massachusetts Institute of Technology |
| 11:00 | Rapid Generation of High Affinity Antibodies from Antibody Secreting Cells after Influenza Booster Vaccination
Using a novel, multiplex PCR-based technique we cloned the variable regions from single ASC isolated 7 days after influenza vaccination and expressed recombinant monoclonal antibodies. With this strategy, we produced over forty human influenza-specific antibodies. This entire process takes less than thirty days and thus represents a substantial technological advance allowing generation of monoclonal antibodies from humans immediately after immunization.
Jens Wrammert, Ph.D., Postdoctoral Fellow, Emory Vaccine Center, Emory University |
| 11:30 | Simultaneous Targeting of Multiple Disease Mediators by a Dual-Specific Ab-like Molecule
For complex diseases involving multiple mediators, simultaneous blockade of multiple targets will likely yield better therapeutic efficacy than inhibition of a single target. We have developed a generally applicable technology for generating a dual-specific, tetravalent IgG-like molecule that can be engineered from any 2 monoclonal antibodies while preserving activities of the parental antibodies. This new molecule can be efficiently produced and exhibits excellent drug-like properties.
Chengbin Wu, Ph.D., Senior Scientist, Abbott Bioresearch Center |
| 12:00 | Technology Workshops
|
|  Efficiency Improvements in the Purification of Novel Antibody Format and Protein-Based Biotherapeutics Using CaptureSelect® Affinity Ligands
We describe methods of purification for various antibody formats and non-antibody protein scaffolds from different source materials using CaptureSelect® affinity ligands. The CaptureSelect® technology is based on the rapid development of highly stable and specific affinity ligands, based on single domain antibody fragments produced in yeasts. BAC provides CaptureSelect® affinity ligands as generic purification tools and as custom tailored purification solutions. We further describe our Yeast Display technology as a tool for the selection of optimal ligand clones and the affinity maturation of biotherapeutic lead molecules.
Pim Hermans, Ph.D., Head of Ligand Discovery, BAC bv (The Bio Affinity Company), The Netherlands |
|  The ADLib® System: Alternative Diversity for Therapeutic Antibody Design
The ADLib system is a novel ex-vivo method for generating monoclonal antibodies. This technology, compared with conventional methods, provides an alternative diversity for acquiring antibodies for unmet therapeutic needs. An antibody library made from a well-established cell line enables isolation of antigen-specific clones rapidly through various approaches, and the obtained antibodies are directly applicable to a variety of functional assays. The ADLib system is a revolutionary platform for therapeutic antibody design.
Masaaki Fujiwara, D.V.M., President and Chief Executive Officer, Chiome Bioscience Inc. |
|  Synthetic Biology and Secretion-Capture Display in Antibody Engineering
Most antibody engineering approaches require the construction of a large number of variant antibodies, followed by selection or screening. Our DNA synthesis, assembly, and error-filtering technology allows us to construct large libraries of genes with defined sequences, with error rates between 1 in 3,000 and 1 in 10,000 base pairs. We have also developed a novel, proprietary protein-display system that captures the secreted protein of interest on the surface of its parent cell.
Dasa Lipovsek, Ph.D., Director of Protein Engineering, Codon Devices, Inc. |
| 12:30 | Networking Luncheon, Last Chance for Exhibit and Poster Viewing |
| 2:00 | Announcements |
| Session VI: Novel Approaches to Enhancing Antibody Potency |
| 2:05 | Chairperson's Opening Remarks
James D. Marks, M.D., Ph.D., Department of Anesthesia and Pharmaceutical Chemistry, Member, Comprehensive Cancer Center, University of California, San Francisco |
| 2:15 | Selecting and Optimizing Breast Cancer Subtype Specific Antibodies for Targeted Nanoliposomal Drug Delivery
To deliver therapeutics into tumor cells, a strategy was developed to select cell binding and internalizing antibodies directly from phage libraries. Using a panel of breast tumor cell lines, we show that breast tumor subtype specific internalizing antibodies can be selected and used to deliver drugs intracellularly. Strategies will be discussed to identify the antigens targeted by antibodies. Cellular uptake can be further optimized by manipulating antibody valency and affinity.
James D. Marks, M.D., Ph.D., Department of Anesthesia and Pharmaceutical Chemistry, Member, Comprehensive Cancer Center, University of California, San Francisco |
| 2:45 | Potent Antibody-Drug Conjugates for Cancer Therapy
Antibody drug conjugates (ADCs) show significant potential for enhancing the antitumor activity of antibodies and for reducing the systemic toxicity of drugs. The therapeutic index of ADCs can be increase by modifying parameters such as drug, linker, drug stoichiometry, and the antibody delivery vehicle. Progress in enhancing the therapeutic index of ADCs is presented.
Paul J. Carter, Ph.D., Vice President, Antibody Technologies, Seattle Genetics, Inc. |
| 3:15 | Targeting Anionic Phospholipids on Tumor Blood Vessels and Viruses
Phosphatidylserine (PS) is absent from the surface of mammalian cells under normal conditions. PS becomes exposed on tumor blood vessels in response to stress conditions in the tumor microenvironment. PS also becomes exposed on virally infected cells and on the outer surface of the virions themselves. A therapeutic monoclonal anti-PS antibody was developed with strong anti-tumor and anti-viral activity in rodent models. Clinical trials are in progress in patients with solid tumors or hepatitis C virus infections.
Philip E. Thorpe, Ph.D., Professor of Pharmacology, Serena S. Simmons Distinguished Chair, University of Texas Southwestern Medical Center |
| 3:45 | Networking Refreshment Break |
| 4:15 | Enhancing the Potency of Therapeutic Monoclonal Antibodies via Fc Optimization
Monoclonal antibodies (mAbs) are used in the treatment of cancer and autoimmune disease. Therapeutic activity of several mAbs depends on cytotoxic activity mediated by molecular interactions of the IgG Fc domains. We will present data on novel IgG Fc domains, identified using a functional genetic screen, with enhanced Fc兛� binding and improved cytotoxic activity. Selected Fc-optimized mAbs outperformed parent antibodies in xenograft tumor models for B cell malignancies and ovarian cancer.
Jeffrey B. Stavenhagen Ph.D., Director Molecular Immunology, Macrogenics, Inc. |
| 4:45 | Enhancing Antibody Potency Using Recombinant Polyclonal Antibodies
Symphogen has developed a method for reproducible production of target-specific fully human recombinant polyclonal antibodies (pAb). The antibodies are isolated from naturally immune human donors. Subsequently, the pAb is expressed using the Sympress platform. Data is presented demonstrating pronounced synergy of antibody mixtures against different categories of antibody targets.
John Haurum, M.D., D.Phil., Chief Scientific Officer, Symphogen A/S, Denmark |
| 5:15 | Manipulating Antibody Affinities to Promote Antibody-Dependent Cellular Cytotoxicity
Increasing the affinity for tumor antigens promotes in vitro antibody-dependent cellular cytotoxicity by recombinant bispecific antibody fragments and intact IgG molecules. We have investigated the relative contributions of affinity for tumor antigens and for human Fc gamma receptor III to promote ADCC, using variants of the C6.5 IgG molecule with differing affinities for c-erbB2 and for human CD16. These studies provide insights into design principles to guide the construction of ADCC-promoting monoclonal antibodies.
Louis M. Weiner, M.D., Vice President, Translational Research; Chairman, Department of Medical Oncology; G. Morris Dorrance Jr. Endowed Chair in Medical Science, Fox Chase Cancer Center |
| 5:45 | Close of Session |
Main Conference - Day Four
Thursday, December 6, 2007
| PRE-CONFERENCE WORKSHOP | DAY ONE | DAY TWO | DAY THREE | DAY FOUR | |
| 7:30 | Networking Coffee |
| 8:00 | Announcements |
| Session VII: Designing Antibodies for Complex Environments |
| 8:05 | Chairperson's Opening Remarks
Richard H.J. Begent, M.D., Head of Oncology, Ronald Raven Professor of Oncology, University College London, United Kingdom |
| 8:15 | Evaluating B-cell Epitope Prediction Tools: Datasets and Metrics
The prediction of B-cell epitopes is highly desirable, but has presented a set of unique challenges to the bioinformatics and immunology communities. Improving the accuracy of B-cell epitope prediction methods depends on community-accepted datasets and metrics to develop and evaluate such tools. Using the Immune Epitope Database, we have assembled several datasets of epitopes corresponding to different prediction tasks, and report the performance of prediction tools to on these sets.
Bjoern Peters, Ph.D., Research Scientist, Immune Epitope Database and Analysis Resource (IEDB), La Jolla Institute for Allergy and Immunology |
| 8:45 | Monoclonal Antibodies Raised to Human Tumor & Tissue Stem Cell Lines Have Anti-Tumor Activity
Antibodies raised to human fetal tissue and tumor stem cell (TSC) were screened for binding against a panel of TSC lines. Twenty-five of these MAbs target antigens present on all of the TSC lines derived from colon, prostate, pancreatic, lung, colon, colorectal, skin, lymphoma and breast cancer. We will discuss the activity of three of these antibodies in in vitro and in vivo models.
Jennie Mather, Ph.D., Founder, President and Chief Scientific Officer, Raven Biotechnologies, Inc. |
| 9:15 | Creating Fusion Proteins for Optimal Function in the Human Physiological Environment and in Tumor
The design of recombinant antibody fusion proteins for cancer treatment is inspired and informed by an understanding of tumor biology and data acquired from pharmacokinetic and molecular models. Using this knowledge, it is possible create multifunctional therapeutics which are effective and practical to produce. The presentation will discuss ways this is achieved using in vitro and in vivo examples of cancer therapeutics built from scFv-enzyme and scFv-albumin fusion proteins.
Kerry Chester, Ph.D., Reader, Department of Oncology, Royal Free and University College Medical School, University College, London, United Kingdom |
| 9:45 | Networking Refreshment Break |
| 10:15 | IMGT, the Informatics Framework to Support Effective Collaboration in Complex Environments
Standardization for genome, proteome, genetics and 3D structure antibody data is required for molecular analysis comparison in complex environments. With its databases, tools and Web resources, based on the IMGT-ONTOLOGY concepts of identification (specificity), description (labels), classification (gene and allele nomenclature) and numerotation (IMGT Colliers de Perles), IMGT®, the international ImMunoGeneTics information system® (http://imgt.cines.fr) provides the informatics framework for standardized molecular characterization of monoclonal therapeutic antibodies.
Marie-Paule Lefranc, Ph.D., Professor, Montpellier University, The University Institute of France, CNRS Institute of Human Genetics, IMGT, France |
| 10:45 | Vascular Targeting with Antibody Derivatives: from the Bench to the Clinic
The antibody-based targeted delivery of bioactive molecules (drugs, radionuclides, cytokines) to the tumor neo-vasculature offers the opportunity to develop biopharmaceutical agents of unprecedented efficacy and selectivity. I will present preclinical and clinical progress made in this field in a collaboration between ETHZ, Philogen, Philochem and Bayer Schering Pharma.
Eveline Trachsel, Ph.D., Head of Therapeutic Antibody Research, Philochem AG, Switzerland |
| 11:15 | Using Targeted Lipidic Nanoparticles for Cell Specific Intracellular Targeting
Liposome-based nanoparticles offer a number of notable advantages as a drug delivery system, and are ideally suited as drug carriers for antibody targeting. We have developed new approaches including new and robust technologies for drug loading and stabilization, resulting in novel "nanoliposome" drugs, and development and optimization of antibody fragment conjugation to generate immunoliposome drugs. These discoveries have led to further development of multiple novel therapeutic agents, including: 1) Anti-HER2 immunoliposome doxorubicin; 2) Anti-EGFR immunoliposome doxorubicin; and 3) nanoliposomal CPT-11.
John W. Park, M.D., Director of Novel Therapeutics, Breast Oncology, University of California San Francisco Comprehensive Cancer Center |
| 11:45 | Lunch on Your Own |
| 1:15 | Announcements |
| Session VIII: CD20-Targeted Antibody Therapeutics |
| 1:20 | Chairperson's Opening Remarks
Louis M. Weiner, M.D., Vice President, Translational Research; Chairman, Department of Medical Oncology; G. Morris Dorrance Jr. Endowed Chair in Medical Science, Fox Chase Cancer Center |
| 1:30 | Topic TBA
Leslie Popplewell, M.D., FACP, Assistant Professor, Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center |
| 2:00 | Optimization of Anti-CD20 Radioimmuno-Drug Delivery - Treatments to Increase Efficacy and Decrease Toxicity
The development of radiolabeled anti-CD20 antibodies (Ab) presents a unique opportunity to treat hematological malignancies by delivering high doses of radiation relatively specifically to sites of disease while sparing normal organs. Despite encouraging results, however, relapse and toxicities remain problems after radioimmunotherapy (RIT). The focus of this presentation is on overcoming these limitations and further improving the therapeutic index (target-to-non-target ratio) over that is currently achievable with conventional anti-CD20 immunoconjugate methodologies.
John Pagel, M.D., Ph.D., Assistant Member, Clinical Research Division, Fred Hutchinson Cancer Research Center |
| 2:30 | Development of Novel Humanized Anti-CD20 Antibodies for Cancer Therapy
To investigate the biological efficacy of new versions of antiCD20 antibodies in eliciting an anti-cancer immunity in lymphoma model systems, we developed several bispecific and tetravalent antibodies, which consisting of two or more binding sites for targeting different epitopes. Results suggest that these antibodies are more effective in killing CD20 positive cell lines, even for those with a low expression of CD20 antigens on the cell surfaces, and may provide a novel strategy for treatment of cancers.
Yajun Guo, M.D., Ph.D., Professor and Director, SMMU Cancer Institute and Shanghai Center for Antibody, China |
| 3:00 | Networking Refreshment Break |
| 3:15 | Modification of Fc Domains to Improve ADCC and Other Effector Functions
Fc gamma receptors (FcgRs) on immune effector cells play an important role in the anti-tumor activities of monoclonal antibodies. We have created variants of the antibody Fc domain with enhanced affinity and selectivity for FcgRIIIa and FcgRIIa. The variants lead to dramatic enhancements in antibody-dependent cellular cytotoxicity (ADCC) and other effector functions. We will discuss application of these variants to various targets such as CD19 and CD40.
John R. Desjarlais, Ph.D., Vice President, Research, Xencor, Inc. |
| 3:45 | Ofatumumab, a Human Antibody Therapeutic Targeting a Novel CD20 Epitope
We generated and characterized a panel of fully human CD20 antibodies. HuMax-CD20 (ofatumumab) has been selected as a lead candidate based on its extraordinary ability to kill tumor cells, including those resistant to rituximab. This talk focuses on its mechanisms of action and differentiation from earlier CD20 antibodies. Studies documenting HuMax-CD20's therapeutic activity in in vivo models and recent data from clinical studies in NHL, B-CLL and rheumatoid arthritis will be discussed.
Jan G. J. van de WInkel, Ph.D., Executive Vice President and Chief Scientific Officer, Genmab, The Netherlands |
| 4:15 | Isotype-Dependent CD20 Mediated B Cell Depletion in Mice and its Effect on the Humoral Response
Anti-CD20 mediated B cell depletion has been shown to be effective in treating rheumatoid arthritis and B-cell malignancies. How this therapy affects a patient's capacity to generate antibody responses is unknown, and safety concerns persist regarding potential immune suppression. Here, we present the B cell depletion characteristics of four isotypes of mouse anti-mouse CD20 with identical variable domains and their effect on the generation of primary and secondary antibody responses.
Robert Dunn, Ph.D., Scientist, Department of Allergy and Asthma, Biogen Idec |
| 4:45 | Close of Meeting |
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