分子重组抗体

4月29日 (二)

1:00 - 2:00pm Registration

CASE STUDIES: RECOMBINANT ANTIBODIES IN THE CLINIC DERIVED FROM PHAGE DISPLAY
(Shared Session with Phage Display of Antibodies and Peptides)

2:00 Chairperson's Remarks
Lutz Jermutus, Ph.D., Director of Research - Technology, MedImmune Ltd. 

2:05 Respiratory Antibody Portfolio Case Study: anti-IL-13, anti-GMCSFR, anti-IL5R, anti-IL-9
Roland Kolbeck, Ph.D., Director, Inflammation & Head, Respiratory Disease, MedImmune, Inc.
Asthma is an inflammatory disorder of the airways associated with airway remodeling, mucus hypersecretion and reversible airway obstruction. Inflammation is characterized by increased numbers of eosinophils, basophils, mast cells and T-helper 2 cells that are a rich source of eicosanoids such as leukotriens and prostaglandins, as well as cytokines such as IL-4, IL-5, IL-9, IL-13 and GM-CSF, each of which orchestrates different aspects of asthma pathology. We have designed specific monoclonal anti-bodies that have been optimized and engineered in ways that allow for the efficient interference with IL-13, IL-9, GMCSFR and IL5R signaling pathways. The relative contribu-tion of either pathway to asthma pathology and the optimization of inhibitory monoclonal antibodies for clinical development will be discussed in detail.

2:50 Dll4 and Notch1 Antagonist Antibodies Inhibit Tumor Growth by Deregulating Angiogenesis
Yan Wu, Ph.D., Senior Scientist, Antibody Engineering, Genentech Inc.
Dll4 (ligand) and Notch1 (receptor) are key molecules for angiogenesis. Activation or over expression of Notch1 is also implicated in many cancers. Blocking Dll4 or Notch1 with specific phage antibodies renders endothelial cells hyperproliferative, and caused defective cell fate specification or differentiation both in vitro and in vivo. In addition, blocking Dll4 or Notch1 inhibited tumor growth in several tumor models.

3:20 DVD-Ig: a Novel Bispecific Antibody Technology
Chengbin Wu, Ph.D., Senior Scientist, Biologics, Abbott Bioresearch Center
Human diseases are often complex and involve multiple disease mediators, therefore drugs that block multiple targets simultaneously will likely yield enhanced therapeutic efficacy. We have developed a novel bispecific antibody technology termed dual-variable domain Ig (DVD-Ig) that can be engineered from any two monoclonal antibodies for targeting two antigens. This new class of molecules can be efficiently produced from mammalian cells and exhibits drug-like properties. Our studies of a DVD-Ig agent in a preclinical animal model demonstrate a strong potential for its therapeutic application in human diseases. 

3:50 Refreshment Break in the Exhibit Hall 

4:15 Case Study: Antibodies as Protease Inhibitors
Laetitia Devy, Ph.D., Principal Scientist, Dyax SA
Antibodies provide the potential for a new generation of protease inhibitors with high levels of potency and selectivity. Combining our human antibody phage display library with automated selection and screening strategies, we have isolated inhibitors of a range of metallo- and serine proteases. We will illustrate this success using DX-2300 and DX-2400. DX-2300 potently inhibits tissue kallikrein 1 (Ki=39 pM) and has demonstrated activity in preclinical models of airway inflammation. DX-2300 has been shown to block kinin generation by tissue kallikrein in vivo and therefore, may be efficacious in various inflammatory diseases. DX-2400 selectively inhibits MMP-14 (Ki=0.8nM), a membrane bound metalloproteinase and has been shown to inhibit tumor progression in different tumor models (MDA-MB-231, MDA-MB-435, BT-474 and PC3). DX-2400 also significantly decreases the incidence of metastases and inhibits tumor angiogenesis. These antibodies represent innovative approaches for the inhibition of key protease regulators of inflammation and cancer.

4:45 Development of a Portfolio of Therapeutic Antibodies for Oncology Combining Xenomouse and Display Technologies
David Blakey, Ph.D., Senior Principal Scientist, Cancer Discovery, AstraZeneca
Astrazeneca has developed a portfolio of antibody-based therapeutics in oncology through its collaboration with Abgenix/Amgen and acquisitions of CAT and Medimmune. Antibodies to some of the target in this portfolio e.g. CD20, ErbB2, MCP1 will be described focusing on differentiation from competitor molecules. The advantages of combin-ing transgenic mouse technology and display technology to yield optimal lead antibodies will be discussed. 

5:15 pm End of Day