2014 Archived Content
Cambridge Healthtech Institute’s Inaugural
Improving the Clinical Efficacy of Antibody Therapeutics
Cutting-Edge Protein Engineering for the Next Generation of
Safe and Effective Biotherapeutics
January 15-16, 2014
At the beginning of 2013, according to one study, there were 350 monoclonal antibodies in development, and therapeutic mAbs have now moved beyond cancer and into a wide range of large disease indications. When these programs advance into the clinic (and some to commercial launch), the quality of therapeutic response will become increasingly important to regulatory agencies and frugal payors. Regulators are becoming more sophisticated in their demands for data to support claims of safety and potency – and payors will seek meaningful therapeutic benefits relative to existing standards of care before adding higher-cost biotherapeutics to formularies. Improving the Clinical Efficacy of Antibody Therapeutics will showcase state-of-the-art discovery and development-stage engineering strategies for improving the safety and effectiveness of this important class of biologic drugs.
Day 1 | Day 2 | Download Engineering Brochure | Speaker Biographies
TUESDAY, JANUARY 14
1:30-2:00 pm Conference Registration
4:30-5:00 Short Course Registration
5:00-8:00 Dinner Short Courses (SC8-SC14) More Details >>
WEDNESDAY, JANUARY 15
7:30 am Conference Registration
8:00 Morning Coffee
8:15 Chairperson’s Opening Remarks
Dimiter S. Dimitrov, Ph.D., Senior Investigator, Protein Interactions Group, National Cancer Institute, NIH
8:20 Coordinated Tumor Growth Suppression via Synergistic Innate and Adaptive Immunotherapy
K. Dane Wittrup, Ph.D., C.P. Dubbs Professor of Chemical Engineering and Biological Engineering, Massachusetts Institute of Technology
We have found that combination treatment with anti-tumor antibody and an IL-2 Fc fusion exerts a significantly stronger suppression of tumor growth than either agent alone. This effect depends on the presence of both CD8+ T cells and neutrophils, indicating a close cooperation between innate and cellular immunity. Strong potential exists for further synergy between antitumor antibodies and the new generation of T cell-directed immunotherapies.
9:00 Antibody-Based Approaches Targeting ERBB2
Mark D. Pegram, M.D., Professor of Medicine, Stanford University Medical Center
9:30 Selection of Isotypes for Immune Modulatory Antibodies
Ann White, Ph.D., Senior Research Fellow, University of Southampton
Recent clinical data have revealed the potential for cancer eradication by immune modulation. Monoclonal antibodies (mAb) designed to block inhibitory signals and stimulate immunity are delivering durable responses; however, their mechanism of action is still not clear. In this talk I will review recent data examining the role of mAb isotype and Fcγ receptor interaction in dictating immunostimulatory and therapeutic activity and discuss ways to optimise these agents through mAb engineering.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Assessing Factors for Predictive Response to ADC Targets in Clinical Tissue for Companion Diagnostic Development
Steven Potts, Ph.D., CEO, Histopathology Services, Flagship Biosciences
Companion diagnostic approaches for ADCs will ideally account not only for the degree of cell surface expression of the target, but also receptor internalization and potential effects of tumor microenvironment. Although in vitro approaches exist to measure these attributes, there are no clinically amenable approaches to measure these critical parameters. This talk will review tissue image analysis approaches that have been designed specifically in context of ADC CDx programs.
11:15 Co-Development of Antibody Therapeutic and Companion Diagnostic for Atherosclerosis Related Cardiovascular Events
Knut Pettersson, Ph.D., Vice President, Preclinical Development, Athera Biotechnologies AB
Phosphorylcholine (PC) is a ‘danger signal’ that is recognized by several receptors of the innate immune system, including natural IgM PC antibodies. Low levels of these antibodies are associated with increased risk for cardiovascular disease (CVD). Here we describe the development of CVDefine™ to measure IgM anti-PC, and a human monoclonal antibody to be used as secondary prevention in CVD patients with low levels of the natural anti-PC.
11:45 Molecular Imaging using Antibodies for Companion Diagnostics
Anna M. Wu, Ph.D., Professor, Molecular and Medical Pharmacology, David Geffen School of Medicine; Founder and Chief Scientist, ImaginAb
Antibodies recognizing cell surface biomarkers have been developed into highly effective therapeutics, and can also form the basis of companion imaging diagnostics. Protein engineering has been employed to tailor pharmacokinetics, control clearance route, and enable site-specific conjugation of radionuclides for non-invasive imaging by SPECT/PET. Importantly, antibody-based imaging provides a broad approach for detection and evaluation based on cell-surface phenotype, providing a versatile tool for assessing disease biology, selecting targeted therapies, and monitoring response to therapy.
12:15 pm Sponsored Presentation (Opportunity Available)
12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
2:00 Chairperson’s Remarks
Greg Adams, Ph.D., Co-Leader - Developmental Therapeutics Program, Fox Chase Cancer Center
2:05 Antibody Mixtures – A Novel Strategy to Treat Cancer
Ivan Horak, M.D., CSO & CMO, Symphogen
Introduction of monoclonal antibodies into the armamentarium of cancer therapeutics dramatically improved outcome of cancer diseases. Thus novel strategies are required to improve outcome of patients with primary resistance as well as acquired resistance. Antibody mixtures provide novel strategy to attack tumor resistance related to receptor or cognate ligand. Targeting several receptors simultaneously may effectively combat tumor plasticity.
2:35 Synthetic Lethality Approach to Anti-EGFR Targeting in Cancer
Igor Astsaturov, M.D., Ph.D., Assistant Professor, Fox Chase Cancer Center
Persistent activity of EGFR and its family members is a common cause for cancer growth and drug resistance. In 2008, we began a series of bioinformatics-guided siRNA library screening experiments to identify novel factors that affect resistance to EGFR. This work established a network of resistance-influencing proteins that included SC4MOL, a little-studied intermediate enzyme in the sterol biosynthesis pathway. Our subsequent detailed analysis of SC4MOL and of a related sterol biosynthetic enzyme, NSDHL showed these enzymes and their substrates dramatically influence EGFR downstream signaling effectors.
3:05 HER2 Antibodies Induce Anticancer Activity with Trastuzumab or Overcome Resistance of Trastuzumab in HER2+ Breast Cancer Cells
Kyu-Tae Kim, Ph.D., Director, Therapeutic Antibodies, AbClon Inc.
AbClon Inc. has discovered new HER2 binders using epitope screening technology and monoclonal antibody technology. We found several HER2 human scFv binders and mouse monoclonal antibodies (mAbs) using HER2-ECD-Fc and the variable regions/CDRs of the mAbs were grafted in human IgG. Cell proliferation assays revealed novel HER2 antibodies either synergistically induce anti-cancer activity with trastuzumab or overcome resistance of trastuzumab in HER2+ breast cancer cells.
3:35 Selected Oral Poster Presentation: Computationally Driven Deimmunization of an ADEPT Enzyme
Karl E. Griswold, Ph.D., Associate Professor, Thayer School of Engineering, Dartmouth College
3:50 Refreshment Break
4:15 Targeting the HER Family Receptors with a Tri-Specific Antibody
Viktor Roschke, Ph.D., Vice President, Biopharmaceutical Research, Zyngenia, Inc.
A tri-specific antibody based construct was generated using the Zybody technology. Cetuximab, a chimeric anti-EGFR monoclonal antibody was used as a scaffold to introduce additional binding specificities. Two peptides, one targeting an alternative epitope on the EGFR molecule and the other specific to HER-3 receptor, were recombinantly fused to the heavy chain of Erbitux. The resulting tri-specific antibody demonstrates activity in the inhibition of signaling pathways and tumor cell proliferation in vitro and shows increased efficacy in xenograft tumor models in vivo.
4:45 Recent Changes in Intellectual Property Law – Will Your Therapeutic Antibody Patents Survive?
John L. Marquardt, Jr., J.D., M.B.A., Ph.D., Attorney at Law, Marquardt Law
The presentation will summarize recent changes in patent law and recent court decisions and discuss the implications for the patentability of therapeutic antibodies, including alternative scaffolds and antibody-drug conjugates. Strategies for obtaining optimal patent protection and ensuring freedom to operate in light of the changes will be presented.
5:15-6:30 Reception in the Exhibit Hall with Poster Viewing
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