2014 Archived Content

Immunogenicity Prediction and Mitigation

Immunogenicity of therapeutic proteins can render the product ineffective and potentially dangerous. Investigators need to know what causes immunogenicity and how to identify immunogenic features to enable them to design their product accordingly. This track will showcase cutting-edge approaches for the identification of risk factors and for designing non-immunogenic biotherapeutics.

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KEYNOTE SESSION: Immunogenicity Reduction and Control

1:30 pm Chairperson’s Opening Remarks

Bonnie RupBonnie Rup, Ph.D., Research Fellow, Immunogenicity Sciences Lead, Pfizer, Inc.


1:40 Measures to Control Immunogenicity to Interferon Beta

Florian DeisenhammerFlorian Deisenhammer, Ph.D., Clinical Department of Neurology, Innsbruck Medical University

We have learned a few lessons as to which factors contribute to immunogenicity of different recombinant preparations of Interferon beta (IFNb), such as route and frequency of administration, drug formulation including pegylation, aggregation, affinity of antibody binding and binding site. Also, patients’ characteristics influence immunogenicity outcomes. How these factors contribute to controlling immunogenicity will be discussed.

2:10 New Approach to B and T Epitope Removal from Immunotoxins with Retention of High Cytotoxic Activity

IraPastanIra Pastan, M.D., NIH Distinguished Investigator, Co-Chief, Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health

Recombinant Immunotoxins are hybrid proteins that kill cancer cells. RITs have produced complete remissions in over 50% of patients with drug resistant Hairy Cell Leukemia with impaired immune systems, but are less active in patients with normal immunity. I will describe new highly active immunotoxins predicted to have low immunogenicity in humans as a result of experimental approaches for the identification and removal of B and T cell epitopes.

2:40 Immunogenicity Risk Assessment Using Human in silico and in vitro Tools


Noel Smith, Ph.D., Senior Group Leader, Lonza Biologics

Incorporating immunogenicity risk assessment into the early stages of development is important for optimal lead selection. This presentation will focus on the human immunogenicity risk assessment platforms at Lonza to aid the selection and optimization of lead candidates. Platforms include Epibase™ in silico for the prediction of T cell epitopes and Epibase™ in vitro for the assessment of T cell and B cell responses in human donor PBMC. 

3:10 Refreshment Break in the Exhibit Hall with Poster Viewing  

4:00 Problem Solving Breakout Discussions

These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

Table: Risk Assessment and Risk Management

Steven J. SwansonModerator: Steven J. Swanson, Ph.D., Executive Director, Medical Sciences (Clinical Immunology), Amgen, Inc.

  • Management in the clinic of products with low and high risk of immunogenicity related adverse events
  • Investigative approaches to consider when only a subpopulation mounts immune responses to a therapeutic protein product
  • Immunogenicity risk assessment as a function of the clinical condition: acute, chronic, malignant, autoimmune etc.
  • Features of a good risk analysis and risk mitigation plan
  • Sharing of experiences of applying risk assessment in pre-clinical and clinical studies

Table: Prediction Technologies for Immunogenicity

Tim HicklingModerator: Tim Hickling, Ph.D., Associate Research Fellow, Pharmacokinetics, Dynamics and Metabolism, Pfizer, Inc

  • Animal models: what aspects can be translated into clinical trials?
  • In silico and in vitro approaches: their benefits separately and in combination
  • Clinical validation of in silico and in vitro tools: which tools withstand the reality check?

Table: Immune Tolerance Approaches

Moderator: Sriram Krishnamoorthy, Ph.D., Scientist, Preclinical and Clinical Development (Hemophilia), Biogen Idec, Inc.

  • Methods for immune tolerance induction
  • The role of T cells in the immune response and the impact of epitope modification
  • Methods for identification and removal of T cell epitopes and evidence for its impact on reducing immunogenicity
  • Tools to use with protein engineering to design non immunogenic biotherapeutics

Table: Measures to Control Immunogenicity to Interferon Beta

Florian Deisenhammer Moderator: Florian Deisenhammer, Ph.D., Clinical Department of Neurology, Innsbruck Medical University

  • Impact of the route and frequency of administration
  • Use of antibody measurements to determine long-term immunogenicity
  • Roles of component peptides in immunogenicity
  • Measures to design drugs with reduced immunogenicity

Table: Aggregates and Other Factors that Impact on Immunogenicity

Moderator: Narendra Chirmule, Ph.D., Executive Director, Clinical Immunology, Amgen, Inc. 

  • What does and does not cause immunogenicity
  • Discussion on the types of aggregate that have been identified: native versus others, clusters versus aggregates, small versus large, high concentration formulation versus less high
  • Factors contributing to aggregation
  • Evidence that indicates that small aggregates act as an adjuvant
  • Risk assessments and risk mitigation plans based on propensity to aggregate
  • Means of mitigating against immunogenicity
  • Is the aggregate induced risk more pronounced for a diseased state
  • Threshold of SVPs that can lead to an inflammatory response

5:00 Close of Day


Recommended Thursday Dinner Short Course* 

Protein Aggregation: Mechanism, Characterization and Immunogenic Consequences - View Detailed Agenda 

*Separate registration required. 


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Immunogenicity for Regulatory Success 

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