2015 Archived Content

Cambridge Healthtech Institute’s Inaugural

Phage & Yeast Display 
噬菌体和酵母展示
Novel Screening * Improved Properties * Challenging Targets

March 31-April 1, 2015

 

Antibody generation, targeting membrane proteins, screening against challenging targets, generating novel constructs such as ADCs and bispecifics are all examples of today’s vast and important applications of screening and display technologies.

CHI’s Phage & Yeast Display conference highlights current and emerging applications and new trends in phage and yeast display and high-throughput screening technologies to discover antibodies and complex proteins with improved properties, and to generate antibodies against intracellular and new infectious diseases targets.

Tuesday, March 31


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7:30 am Registration and Morning Coffee

8:50 Chairperson’s Opening Remarks

Jonas V. Schaefer, Ph.D., Head, High-Throughput Laboratory, Department of Biochemistry, University of Zurich, Switzerland


NOVEL DISCOVERY AND SCREENING STRATEGIES

CaseStudy9:00 Novel Fully Human Antibody Development Towards Immune Regulators 

Yan LuanYan Luan, Ph.D., Director, DingFu Biotarget Co.

Novel fully human antibodies targeting immune checkpoints were developed by yeast display systems. My presentation will includes a platform introduction as well as Case study about PD-L1 antagonist Ab development. Both biology and developability are considered and evaluated. 

 

9:30 Drug Discovery Using a Modular Antibody Platform™

HaijunSunHaijun Sun, Ph.D., Vice President, Tumor Biology and Protein Sciences, F-Star Biotechnology, United Kingdom

In this presentation, we will discuss our Modular Antibody Platform and highlight some of the key steps during the discovery phase to select the best monospecific or bispecific therapeutic candidates. Several case studies from preclinical programs will be discussed.

10:00 Establishment of an Innovative High-Throughput Platform for Next-Generation Binder Discovery

JonasSchaeferJonas V. Schaefer, Ph.D., Head, High-Throughput Laboratory, Department of Biochemistry, University of Zurich, Switzerland

To optimize the efficiency and capacity of next-generation binder selections and discovery, our laboratory established a streamlined process, consisting of parallel Ribosome Display selections and various semi-automated high-throughput screenings. We now can perform simultaneous selections against 94 targets and subsequently screen and validate several thousand binders in parallel for their binding and biophysical characteristics. This results in the need of testing fewer candidates to eventually find the most promising lead candidates.

10:30 Coffee Break


ANTIBODIES AGAINST COMPLEX & CHALLENGING TARGETS

11:00 Strategy for Identifying Allosteric Antibodies that Modulate Membrane Receptors

MichelleShenMichelle Yuqing Shen, M.D., MSc., MBA, Senior Scientist, Amgen China R&D

We developed a screening strategy using in vitro cell-based assays to identify antibodies that enhanced endogenous ligand signaling. Furthermore, we applied binding assays to reveal those antibodies that do not compete with endogenous ligand binding to receptors. This mechanism of action leverages on enhancement of endogenous ligand signaling while offers greater receptor selectivity and better safety profile owing to allosteric binding to receptors and modulators’ ceiling effect.

11:30 Generation and Optimization of Nanoparticle Targeting Antibodies

LihuiXuLihui Xu, Associated Director and Antibody Technology Team Leader, Merrimack Pharmaceuticals

Antibody targeted nanoparticles have the potential to increase the therapeutic index of cytotoxic anti-cancer therapies by directing them to tumor cells, however the targeting antibody fragment requires careful engineering as multiple parameters need to be optimized. We developed a yeast display platform for antibody generation, and will present a case study of comprehensive scFv antibody engineering for use as a targeting arm of a liposomal cytotoxic nanoparticle. 



12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Networking Luncheon

1:45 Chairperson’s Remarks

Jonas V. Schaefer, Ph.D., Head, High-Throughput Laboratory, Department of Biochemistry, University of Zurich, Switzerland


ANTIBODIES AGAINST INFECTIOUS DISEASES

1:50 Synthetic Antibodies for Ebola Virus Immunotherapy and Research

JonathanLaiJonathan R. Lai, Ph.D., Associate Professor, Biochemistry, Albert Einstein College of Medicine

Synthetic antibody engineering is an emerging technology for the identification of highly specific antibodies from large molecular display libraries. Here, we will show the application of this method to discover potential immunotherapies and research reagents for Ebola virus. We have identified novel synthetic antibodies against the glycoproteins of the Zaire (EBOV) and Sudan (SUDV) Ebolavirus species. These antibodies have neutralization potential and, in the case of SUDV, afford post-exposure protection of mice.

2:20 Novel Strategies for Isolation of Antibodies Against Infectious Disease Targets

StephenMahlerStephen Mahler, Ph.D., Professor, Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Australia

Using either immunised or naïve libraries and phage display technology, we demonstrate novel strategies for isolation of antibodies that bind immunodominant and non-immunodominant epitopes of viral antigens. The strategies include biopanning against recombinant viral antigens, peptides, antigens expressed on host cell surface and also the use of molecular scaffolds to display viral protein domains. Strategies for isolation of novel antibodies that bind Dengue and Malaria antigens are presented.

2:50 The Development of Antibody-Based Therapeutics for the Treatment of Emerging Infectious Diseases

TianleiYingTianlei Ying, Ph.D., Head, Antibody Engineering and Drug Discovery Group, School of Basic Medical Science, Fudan University

Emerging infectious diseases are currently the major threat to public health. By using human antibody libraries and in vitro display technologies we have identified potent neutralizing antibodies against some new viruses including MERS-CoV and avian influenza viruses. We also have been working on the engineering of novel antibody fragments with small size and long in vivo half-lives.

3:20 Sponsored Presentation (Opportunity Available)

3:50 Refreshment Break



Plenary Keynote Session

4:35 Keynote Introductions

Weidong Jiang, Ph.D., CSO, Henlius Biopharmaceuticals, Inc.

 CaseAndUnpub_Plenary4:40 Antibody Development Strategies in Today’s China

Chengbin WuChengbin Wu, Ph.D., President, R&D and CSO, Shanghai C.P. Guojian Pharamceutical Co. Ltd., PR China

In the past 10 years, commercial manufacturing of antibodies at GMP standard has become possible in China, leading to successful commercialization of several antibody-based therapeutics, with many more in various stages of development. This talk will provide a brief overview of antibody development in China, with a case study discussing key aspects of developing an anti-Her2 antibody that has completed Phase III clinical trials in China.

5:10 Designing and Engineering Novel Bispecific/Bifunctional Antibodies and Fusion Proteins for Enhanced Antitumor Activity

Zhenping ZhuZhenping Zhu, Ph.D., Executive Vice President, Global Biopharmaceuticals, Kadmon Corporation

Major obstacles in the successful development of BsAb (bispecific antibodies) have been the difficulties of designing and constructing a druggable molecule and producing sufficient materials for development and commercialization. The technological challenge is to construct a recombinant molecule with good pharmaceutical properties. Developing highly effective BsAb and bifunctional proteins will require clear elucidation and understanding of the molecular details in the aberrant signaling pathways that lead to various diseases to guide the selection of the target pairs for co-targeting.


5:40 Welcome Reception in the Exhibit Hall with Poster Viewing

6:40 Close of Day

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Wednesday, April 1

 

 

8:30 am Registration and Morning Coffee

8:50 Chairperson’s Opening Remarks

Daniel Christ, Ph.D., Associate Professor & Head, Antibody Therapeutics, Immunology Program, Garvan institute of Medical Research, Australia


GENERATING ANTIBODIES AND COMPLEX PROTEINS WITH IMPROVED PROPERTIES

9:00 Stable Human Antibody Therapeutics and Biobetters through Engineering of Complementarity Determining Regions

DanielChristDaniel Christ, Ph.D., Associate Professor & Head, Antibody Therapeutics, Immunology Program, Garvan institute of Medical Research, Australia

We have recently identified aggregation hotspots in the CDR regions of antibody variable domains, and have developed generally applicable phage display strategies to overcome these limitations. Here we outline the application of the technology to human IgG antibody therapeutics, and present examples of how the approach can be utilised for the ‘retrofitting’ of preclinical and clinical candidate molecules, as well as biobetters.

9:30 Identification of Myeloid-Derived Suppressor Cell-Specific Targets by Phage Display

HongQinHong Qin, M.D., Ph.D., Assistant Professor, Lymphoma & Myeloma, MD Anderson Cancer Center

We identified two novel, mouse MDSC-specific peptides using phage display technology. The engineered peptides (peptibodies) efficiently depleted systemic and intratumoral MDSC in tumor-bearing mice, but did not affect other proinflammatory cell types. Proteomic analysis of cell surface membrane proteins precipitated by the peptibodies suggests that the lead candidate target on the surface of MDSC is S100 family proteins (S100A9/A8). Hence, we developed a technical platform of cell-specific marker discovery.

10:00 Sponsored Presentation (Opportunity Available)

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

CaseStudy11:10 Affinity Matured Anti-Tacrolimus Antibody for Improved Immunoassay Performance

BailinTuBailin Tu, Ph.D., Principal Scientist, Biologics Discovery and Design, Abbott Laboratories

We screened and isolated scFv clones from diverse libraries with mutagenic complementarity regions (CDRs) from anti-tacrolimus hybridoma cell line using yeast display. Various combinatorial pairings constructed from these individual mutations contained >10-fold improvements in both the dissociation rate and overall equilibrium affinity constants. Selected clones produced as IgG have increased functional sensitivity, with a 3- to 6-fold better performance relative to the parental tacrolimus monoclonal antibody.

CaseStudyandUnpub11:40 Employing Immune Tolerance Breaking Technology to Obtain Antibodies with Improved PK/PD Properties

XuemingQianXueming Qian, Ph.D., Chairman and CEO, Mabspace Biosciences, Co. Ltd., PR China

Generating antibodies with improved PK/PD properties is an important goal for developing a differentiated and competitive antibody product. We employ immune tolerance breaking technology to obtain antibodies targeting diverse epitope space, enabling the selection of antibodies with improved biological activities, improved manufacturability or pH-dependent binding to enable recycling. Case studies will be presented for fast follow-on antibody programs targeting PDL-1 and VEGFR2, two important proteins regulating tumor microenvironment.

UnpublishedData12:10 pm Igy Antibody Engineering, More Than Antibody Extraction from Egg Yolk

XiaYingZhangXiaoYing Zhang, Ph.D., Professor, Veterinary Pharmacology, College of Veterinary Medicine, Northwest A&F University

Avian IgY antibodies have been generated against conserved mammalian antigens with high titer and specificity, and also successfully developed to detect small molecules in nano-molar range/mL. mIgY antibodies can be effectively used in certain applications like immunological detection and diagnosis, screening and validating biomarkers, and drug targets. mIgY antibodies are developed by phage display technology. And these can be developed into Ab fragments, chimeric Abs and humanized Abs.

12:40 Networking Luncheon in the Exhibit Hall with Poster Viewing and Close of Phage & Yeast Display Conference



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Celebrating 25 Years


Track 1

Protein & Antibody Engineering

Track 2

Protein Aggregation & Stability

Track 3

Immuno-Oncology

Track 4

Analytical Characterization of Biotherapeutics