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Cambridge Healthtech Institute’s 2nd Annual
Improving the Clinical Efficacy of Antibody Therapeutics
Cutting-Edge Protein Engineering for the Next Generation of
Safe and Effective Biotherapeutics

January 22-23, 2015


When the more than 350 therapeutic monoclonal antibodies in development advance into the clinic and to commercial launch, the quality of therapeutic response will become increasingly important to regulatory agencies and frugal payers. Regulators are demanding better data to support claims of safety and potency – and payers are seeking meaningful therapeutic benefits relative to existing standards of care before adding higher-cost biotherapeutics to formularies. The Improving the Clinical Efficacy of Antibody Therapeutics conference showcases state-of-the-art discovery and development-stage engineering strategies for improving the safety and effectiveness of this important class of biologic drugs.


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Final Agenda 


THURSDAY, JANUARY 22

11:30 am Conference Registration

12:30 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:30 Ice Cream Break in the Exhibit Hall with Poster Viewing


Glycoengineering and Enhancing
Effector Function

2:00 Chairperson’s Opening Remarks

Janine Schuurman, Ph.D., Vice President, Research, Genmab


Keynote Presentation

2:05 A Palette of Engineered Fc Domains for Optimal Antibody-Mediated Target Cell Clearing and Immunomodulation

George Georgiou, Ph.D., Professor, Cockrell Family Regent’s Chair in Engineering, Department of Biomedical Engineering, The University of Texas at Austin

We have engineered a variety of aglycosylated Fc domains displaying: (i) very high binding affinity and selectivity for each individual human Fcγ receptor; (ii) Fc domains that bind only to C1q; (iii) to Fcγ receptors as well the FcγRI receptor that binds to IgA. These Fc domains were shown to elicit unique profiles of immune cell activation and the clearance of target cells.


2:45 Improving the Therapeutic Efficacy of pH and Calcium-Dependent Antigen Binding Antibodies

Tomoyuki Igawa, Ph.D., Group Manager, Discovery Research, Chugai Pharmaceutical Company

pH or calcium-dependent antigen binding antibody enhances antigen elimination by dissociating the antigen in the endosome. Here we report that Fc receptors such as FcRn and inhibitory FcgRIIB can be exploited to further accelerate the antigen elimination by pH or calcium-dependent antigen binding antibody. Enhancing binding to Fc receptors, either by Fc engineering or by formation of multimeric antibody-antigen complex, significantly accelerated antigen elimination from plasma in vivo.

3:15 Glycoengineering Enhanced ADCC in a FGFR2b-Specific Antibody Treating Patients with Gastric Cancers

Kristen Pierce, Ph.D., Associate Director, Oncology, Five Prime Therapeutics

3:45 Sponsored Presentation (Opportunity Available)

4:15 Refreshment Break in the Exhibit Hall with Poster Viewing

5:00 Complement Is Activated by IgG Hexamers Assembled at the Cell Surface

Janine Schuurman, Ph.D., Vice President, Research, Genmab

Complement activation by antibodies is an important mechanism in immune defense and immunotherapy. Using X-ray crystallography, mutagenesis studies and cryo-EM tomography, we revealed that IgG antibodies form hexamers on the cell surface following antigen binding. Enhancing hexamerisation on the cell surface by using the HexaBodyTM platform potentiated the intrinsic killing capability of antibodies in in vitro, in vivo and ex vivo models.

5:30 Cytotoxic Mechanisms of Immunotherapy: Harnessing Complement in the Action of Anti-Tumor Monoclonal Antibodies

Ronald P. Taylor, Ph.D., Professor of Biochemistry, University of Virginia

We followed CDC mediated by CD20 mAbs engineered to enhance Fc-Fc contacts, thus promoting strong C1q binding and rapid CDC. Confocal microscopy movies revealed that during CDC, Ca2+ rapidly enters cells and is soon localized to mitochondria. Ca2+ poisoning likely is the most proximate mediator of cytotoxicity. These observations should allow for deeper understanding of CDC mechanisms, and will play a critical role in development of more effective immunotherapeutic mAbs.

6:00-7:00 Reception at the Tiki Pavilion



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