Digital Course: Immunogenicity Prediction and Mitigation

CONFERENCE SERIES: Bioprocess and Manufacturing

Recorded at: Immunogenicity Summit

Order DVDImmunogenicity Prediction and Mitigation DVD Cover About this Product: 

A 180 minute digital course consisting of six important presentations from the Immunogenicity Summit in Bethesda in November 2011. Questions from the audience and the replies are included. Features presentations from the FDA, from the European Immunogenicity Platform, from the Laboratory of Huub Schellekens, from the Uniformed Services University and from Pfizer and Antitope.




About this Product:
6 Presentations
193 Slides
Over 191 Minutes
Individual: $345
Site License: $1380  

Agenda At A Glance: 


Coupling of Aggregation and Immunogenicity in Biotherapeutics: T- & B-Cell Immune Epitopes May Contain Aggregation Prone Regions
Sandeep KumarSandeep Kumar, Ph.D., Principal Scientist, Biotherapeutics Pharmaceutical Sciences, Pfizer, Inc.
In this talk I shall describe a potential coupling between aggregation and immunogenicity: T-cell and B-cell immune epitopes in therapeutic proteins may contain aggregation prone regions. The details of biological mechanisms behind this observation remain to be understood. However, this observation opens up an exciting potential for rational design of de-immunized novel, as well as follow on, biotherapeutics with reduced aggregation propensity.

Biography: Sandeep Kumar is interested in protein structure-function relationships. He received his Ph.D. Computational Molecular Biophysics from Indian Institute of Science, Bangalore and performed postdoctoral research on protein stability at National Cancer Institute -Frederick. Between 2002 and 2007, Sandeep served worked at Georgetown Univ., Indian Institute of Technology-Kanpur and Johns Hopkins University. Sandeep joined Pfizer in 2007 and has been involved in computational modeling of biotherapeutic drug candidates. He has been working on issues related to aggregation, immunogenicity, disulfide bond scrambling and other physico-chemical liabilities in therapeutic antibodies. Sandeep has been promoting cost-saving, rational structure based strategies for design and selection of highly potent biotherapeutics with improved stability and safety. Sandeep has contributed towards 43 research papers, review articles and book chapters so far.

Innate Immune Response Modulating Impurities
Daniela VerthelyiDaniela Verthelyi, M.D., Ph.D., Chief, Laboratory of Immunology, Therapeutic Proteins, CDER, FDA
Immune cells express numerous receptors that respond to conserved molecular patterns present in pathogens as well as in stressed tissues. This talk will review recent data, present a few cases, and discuss the role of trace levels of impurities in therapeutic proteins that stimulate the innate immune response in facilitating an immunogenic response to therapeutic proteins. 

Biography: Dr. Verthelyi received her MD from the University of Buenos Aires and a PhD from the Virginia Tech in USA, and then completed a fellowship training in Immunology at the Section in Retroviral Immunology of the Center for Biologics Evaluation and Research of the FDA before joining the Laboratory of Immunology of Division of Therapeutic Proteins and eventually becoming its Chief. Dr Verthelyi’s laboratory, established in 2002, studies innate immune response modulators in several disease models.  She has authored over 50 peer reviewed articles, chairs the NIH/FDA Cytokine interest Group, and received of the FDA's ‘Excellence in Laboratory Sciences Award, among other honors.

Our studies have centered on understanding the differential responses of TLR9 agonists and develop synthetic agonists that can act as immunoprotective agents for cancer and infection, and as vaccine adjuvants.  Over the years we have developed novel chemistry to allow for effective CpG ODN treatment in primates,  the first primate model to assess TLR9-mediated immunoprotection by CpG ODN, established that CpG ODN can enhance immune function in HIV-infected and other immunocompromised patient populations, and determined that direct modulation of the immune response can reduce the severity of viral encephalitis.  Our current studies are focused on the understanding the impact of TLR-stimulating impurities in product immunogenicity.


Recommended Strategies for the Assessment of Protein Aggregates in Pharmaceutical Biotech Product Development
John EngelsmanJohn den Engelsman, Ph.D., Analytical Development and Validation, Merck, Sharpe & Dohme
Within the European Immunogenicity Platform (EIP) (, the Protein Characterization Subcommittee (EIP-PCS) has been established to discuss and exchange experience of protein characterization in relation to immunogenicity. This group has reviewed the current state of methods for analysis of protein aggregates. This talk elaborates on why these methods should be used and makes recommendations regarding strategies for their application during the development of protein therapeutics.

Biography: Dr. John den Engelsman received an M.Sc. from Leiden University in the field of molecular cell biology. He received a Ph.D. in biochemistry from the Radboud University of Nijmegen, where he worked on the purification and cellular trafficking of chaperone proteins. Dr. den Engelsman joined NV Organon in 2006 as a scientist. In 2006 he became a groupleader at NV Organon responsible for biophysical characterization and (pre-)formulation development. He is currently a senior scientist and section head (biophysical characterization) at the department of Analytical Development and Validation at MSD.

Tools, Tools, Tools and even more Tools! How to Predict Immunogenicity in Silico, in Vitro and in Vivo – an Overview   
Melody SauerbornMelody Sauerborn. Ph.D., Pharmaceutical Sciences, University of Utrecht, and CEO, ADA InVivo BV
New analytical tools have been implemented in drug development processes to detect and characterize drug aggregates. Besides analytical tools, the industry uses biological tools such as in silico, in vitro and in vivo to predict immunogenicity of protein drugs. This presentation gives an overview about the currently used biological tools and discusses their pro and cons.

Biography: Dr. Sauerborn spent most of her undergrad years in well-known institutes such as the Centers for Disease Control and Prevention in Atlanta to widen her knowledge in immunology and hemorrhagic fever viruses. After acquiring her Masters in Infectious Diseases she joined the lab of Prof. Schellekens and Prof. Jiskoot, two experts in immunogenicity of recombinant human therapeutics, to shed more light on the immunological aspects of antibody formation against aggregated protein therapeutics. Based on her promising data obtained during her PhD she recently started a spin-off, ADA InVivo BV. ADA InVivo is the first company offering in vivo immunogenicity testing of protein drugs.


Advances in Abrogating Immunogenicity with Fc Fusion Proteins
David ScottDavid W. Scott, Ph.D., Professor & Vice Chair, Research, Department of Medicine, Uniformed Services, University of Health Sciences, Bethesda
Tolerance induction using IgG and Fc conjugated fusion proteins has been studied for over three decades. This talk will explore the basis of this tolerogenicity and its application using different modes of presentation to the immune system. The mapping and recognition of potentially tolerogenic peptides in therapeutic proteins will be emphasized. Possible mechanisms for their success and applications for the future will be discussed. 

Biography: David W. Scott, Ph.D. is Vice Chair for Research in the Department of Medicine at the Uniformed Services School of Health Sciences (USUHS) in Bethesda, MD. An alumnus of Antioch College, Dr. Scott received his M.S. degree from the University of Chicago and Ph.D. from Yale University in 1969. Following a post-doctoral fellowship at Oxford University, UK, he joined the faculty at Duke University in 1971, where he initiated his NIH-funded studies on immune tolerance mechanisms. In 1983, he was named Dean's Professor of Immunology at the University of Rochester, a post he held for 11 winters. Dr. Scott thereafter became Head of the newly formed Immunology Department at the Holland Lab of the American Red Cross, and moved to the University of Maryland School of Medicine in 2004. He assumed his current position at USUHS in September 2010.

Dr. Scott has contributed to over 200 research papers on several subjects in immunology, focusing on immunologic tolerance, and its application in autoimmune diseases, hemophilia and gene therapy. He is the author of two textbooks, including a monograph entitled, The Nature of Immunologic Tolerance, and recipient of a number of awards, including the Distinguished Service Award, from the American Association of Immunologists (2004), a Boerhaave Professorship at Leiden University Medical School, The Netherlands (2006) and the 2009 Scientific Achievement Award from the AAPS.

Active in science education, Dr. Scott has been chair of Education committees at the ASM and AAI. He has also served on the editorial boards of major immunologic journals, and as a member of NMSS, JDRF and NIH Study Sections.

New Data on the Impact of T Epitope Removal on Immunogenicity and Aggregate Formation
Matthew BakerMatthew Baker, Ph.D., CSO, Antitope Ltd. 
The focus of this presentation will be to provide case study examples of how technologies to measure and quantify T cell epitopes can be applied to select protein therapeutics with a reduced risk of immunogenicity. Furthermore new data will be presented on how aggregates in some formulations can trigger innate responses that ultimately enhance T cell immunogenicity in vitro.

Biography: Dr Baker is a founder and the Chief Scientific Officer of Antitope Ltd, a Cambridge (UK) based company which specializes in assessing and reducing the immunogenic potential of biologics. He has held senior management positions at a number of companies including Biovation (subsidiary of Merck KGaA), CTL Ltd and Whatman BioSciences. As an academic researcher Dr Baker has a background in B and T cell immunology and completed post-doctoral positions in Cambridge, UK after obtaining his PhD in cellular immunology at University of Birmingham, UK.

About the Conference: 

The talks in this digital course examine the various factors that contribute to immunogenicity of biotherapeutics, particularly aggregates, sub-visible particles and other impurities, and on the role of T and B cell epitopes in the elicitation of an immune response. This is followed by a review of the current approaches for assessing and characterizing protein aggregates and immune-response stimulating features with a view to predicting immunogenicity of biotherapeutic products.  Finally there is a session on means to reduce immunogenicity by introducing tolerogenic peptides and selection of proteins with reduced immunogenicity.

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