Cambridge Healthtech Institute's 19th Annual

Engineering Antibodies

( 抗体のエンジニアリング )

次世代の治療用抗体と生物学的製剤の選択、エンジニアリング、標的指向化のための新たな研究と技術

2018年5月2-3日 | World Trade Center | マサチューセッツ州ボストン

 

The field of protein engineering is at an exciting point in its development, with new generations of therapeutic antibodies now reaching the market, great advances in protein science, and a body of clinical evidence that can be used to inform the development of safe, highly effective therapies for unmet medical needs. The PEGS Engineering Antibodies conference explores case examples of the most significant emerging technologies used by protein engineers working at the discovery and design stages to quickly and efficiently craft biotherapeutics directed at the most elusive targets and biological functions.

Final Agenda

Recommended Short Course(s)*

SC8: Introduction to Biophysical Analysis for Biotherapeutics: Discovery & Development Applications


*Separate registration required.

5月2日 (水)

7:30 am Registration and Morning Coffee

困難な標的に対応する抗体

8:30 Chairperson’s Remarks

Jonas Schaefer, PhD, Head, High-Throughput Binder Selection Facility, Biochemistry, University of Zurich, Switzerland

8:40 Anti-RAS DARPins as Multipurpose Tools to Investigate Its Versatile Functions and to Design Novel Approaches to Make It a Druggable Target

Jonas SchaeferJonas Schaefer, PhD, Head, High-Throughput Binder Selection Facility, Biochemistry, University of Zurich, Switzerland

Even after decades of research, a direct inhibition of the high-priority anticancer drug target KRAS with small molecules has been extremely challenging. Therefore, DARPins - very potent proteinaceous binders with highly beneficial properties - were generated to bind to various sites of oncogenic Ras mutants, thus efficiently interfering with the numerous interactions with their effector proteins. These DARPins might therefore help to investigate various approaches to attack this so far ‘undruggable’ target.

9:10 New Strategies to Identify Functional Antibodies against Complex Membrane Proteins

JT Koerber, PhD, Scientist, Antibody Engineering, Genentech

Integral membrane proteins comprise a large untapped target space for therapeutic antibodies, but the discovery of functional antibodies against this class of proteins remains a challenge. The dynamic nature of these targets coupled with complex functional assays can limit the efficiency of all project stages from initial discovery to ultimately characterization of lead antibodies. I will discuss our efforts towards addressing these challenges.

9:40 Engineering Strategies to Enhance Antibody Specificity toward MHC-Peptide Complex

Andy YeungAndy Yeung, PhD, Associate Research Fellow, Rinat, Oncology R&D, Pfizer, Inc.

A panel of antibodies targeting a MHC-peptide complex implicated in cancer was isolated using phage display. While the crystal structure illustrates that the lead clone binds MHC-target-peptide complex in a TCR-like manner, the clone also demonstrates undesired cross-reactivity to several sequence-similar off-target peptides, which were computed using human genome. Using both computation and structural information, we were able to improve the specificity of the antibody by engineering out the cross-specificity.

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

特異抗体の発見

10:55 Structure-Function Analysis to Identify Rare Epitopes with Unique Binding Properties

Bruno CorreiaBruno Correia, PhD, Professor, Protein Design and Immunoengineering, EPFL Zurich, Switzerland

We developed a computational design strategy with the ultimate goal of designing accurate epitope mimics for the development of novel vaccine candidates. Recently, a first proof of principle has shown that a computationally designed protein presenting the Respiratory Syncytial Virus (RSV) Motavizumab epitope elicited potent neutralizing antibodies in nonhuman primates. We have extended this approach to several epitopes in RSV, and I will present biochemical, biophysical and immunological characterization of the computationally designed immunogens.

11:25 Discovery of High-Affinity Human PD-1 and LAG-3 Antibodies Using Novel Microfluidic and Molecular Genomic Methods

David S. JohnsonDavid S. Johnson, PhD, CEO, GigaGen

Conventionally, mouse hybridomas or well-plate screening are used to identify therapeutic monoclonal antibody candidates. We have developed a novel alternative to hybridoma-based discovery that combines microfluidics, yeast single chain variable fragment (scFv) display, and deep sequencing. We have used our technology to rapidly discover thousands of checkpoint inhibitor candidates against sixteen targets, in less than six months. In this talk, we will specifically focus on our PD-1 and LAG-3 programs.

11:55 KEYNOTE PRESENTATION: The “Fit for Purpose” Decision Tree in Selecting a Product Strategy for a Target Candidate

Lioudmila Tchistiakova, PhD, Senior Director, Global Biotherapeutic Technologies, Pfizer

During the transition from discovery into development, important decisions must be made about the modality that will be used for a lead target candidate. This talk will review Pfizer’s approach to this process and offer case examples that demonstrate the options available for large molecules and the variables that are considered as part of our selection process.

 

12:25 pm Talk Title to be Announced

Pierre-Alain Girod, PhD, CSO, Selexis SA

 

12:55 Luncheon Presentation I: Rapid Purification, Concentration, and Characterization of Antibodies and Proteins: Capturem High-Capacity Membranes

Tim Larson, PhD, Marketing Specialist I, Marketing, Takara Bio USA

We have developed Capturem technology, a novel, nylon membrane-based system with an extremely fast workflow that can be completed in 5-20 minutes, with the added benefit of resulting in an exceptionally pure and concentrated eluate in single column and high-throughput formats. We have also demonstrated trypsin and pepsin-functionalized membranes for rapid protein digestion for downstream analysis. Capturem membranes can dramatically speed up product development by eliminating the long incubation times required with traditional workflows.

1:25 Luncheon Presentation II (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:55 Session Break

選択的結合のエンジニアリング

2:10 Chairperson’s Remarks

Danlin YangDanlin Yang, PhD, Scientist, Biotherapeutics Discovery, Boehringer Ingelheim


2:15 Receptor Engineering and Strategies for Selective Binding

Joel Cohen-SolalJoel Cohen-Solal, PhD, Senior Research Scientist, Global Protein Sciences, AbbVie Bioresearch Center

Binding studies of IgG-based biologics to Fc Receptors carried out by cell-based assays are valuable to better characterize the interactions in physiologic-like settings and to identify parameters for selective binding.

2:45 Maximizing in vivo Target Clearance by Design of pH-Dependent Target Binding Antibodies with Altered Affinity to FcRn

Danlin YangDanlin Yang, PhD, Scientist, Biotherapeutics Discovery, Boehringer Ingelheim

In the past five years, the concept of recycling and sweeping antibodies has emerged in the literature. These antibodies have demonstrated potential success in reducing target levels compared to conventional antibodies. Here we present the groundwork on how to maximize target reduction through the optimal design of binding kinetics and pH-dependence to both antigen and FcRn in the therapeutic candidate, potentially providing a path to greater patient dosing convenience.

3:15 Sponsored Presentation (Opportunity Available)

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing

4:45 Problem-Solving Breakout Discussions

5:45 Networking Reception in the Exhibit Hall with Poster Viewing

7:00 End of Day

5月3日 (木)

8:00 am Morning Coffee

特性の改善を目的とした抗体のエンジニアリング

8:30 Chairperson’s Remarks

Caroline ColleyCaroline Colley, PhD, Associate Director, Antibody Discovery and Protein Engineering, MedImmune, United Kingdom


8:35 Agonizing the TNFR Superfamily for Cancer Immunotherapy

Greg LazarGreg Lazar, PhD, Director, Antibody Engineering, Genentech

Multiple technology platforms have been explored to enable antibodies to mediate receptor agonist activity without relying on Fc receptor-mediated crosslinking. This talk will describe engineering approaches and considerations, present data demonstrating in vitro and in vivo proof-of-concept, and discuss biological and clinical context as they relate to cancer immunotherapy.

9:05 Strategies for Identifying Biologics with Specific Mechanisms of Action

Caroline ColleyCaroline Colley, PhD, Associate Director, Antibody Discovery and Protein Engineering, MedImmune, United Kingdom

In biologics discovery, assay cascades can be designed from the outset to triage thousands of antibodies for the desired function, specificity and affinity. While early functional screening is paramount, it is also important to understand the mechanism of action through which an antibody mediates its effects (e.g. competitive, allosteric), to ensure appropriate target suppression. Using case studies, strategies and learnings for identifying antibodies with the desired mechanism will be highlighted.

 

9:35 Presentation to be Announced

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

11:05 Fc Engineering for Complement-Mediated Effector Function and FcRn-Mediated Pharmacokinetics

Chang-Han LeeChang-Han Lee, PhD, Postdoctoral Researcher, Georgiou Lab, The University of Texas at Austin

Engineered Fc domains, which have an asymmetric structure and completely selective binding to C1q without any concomitant FcγR engagement, were used to demonstrate that CDCC and CDCP of therapeutic antibodies mediate removal of target cells with equivalent kinetics and potency as FcγR-dependent ADCC and ADCP mechanisms in vitro and in mouse models. In another engineered Fc domain, it showed enhanced serum half-life in several hFcRn mouse models and is applicable for IgG subclasses.

11:35 Engineering Antibodies for Tissue Specific Inhibition

Gregory CarvenGregory Carven, PhD, Vice President, Antibody Discovery & Protein Sciences, Scholar Rock

Traditional therapeutic approaches directly target a growth factor or its receptor everywhere in the body, not only shutting down its harmful function in disease, but also potentially causing undesirable side effects arising from the inherent biology of growth factors. Individual growth factors occur as members of larger families of structurally related proteins, and a single growth factor can lead to a different biological effect in different tissues. By intervening in supracellular activation, our medicines target growth factors in their latent, inactive forms to selectively and locally modulate growth factor activity.

12:05 pm Designer Proteins: Targeting Protein-Pathogen Interactions

Eva-Maria Strauch, PhD, Research Assistant Professor, Biochemistry, University of Washington

Many viral surface glycoproteins and cell surface receptors are homo-oligomers, and hence can potentially be targeted by geometrically matched homo-oligomers. I will describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites. I will conclude with how we can take the design of binding proteins to the next level using completely customized, de novo designed proteins against pathogens.

12:35 End of Engineering Antibodies

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

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