Immunogenicity Prediction and Mitigation
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Part One | Part Two
FRIDAY, October 12
8:30 am Chairperson’s Remarks
Wim Jiskoot, Ph.D., Professor, Division of Drug Delivery Technology, Leiden University
8:35 Predictive Immunogenicity Assessment Strategies to Reduce Immunogenicity Risk to Biotherapeutics
Vibha Jawa, Ph.D., Principal Scientist, Clinical Immunology, Amgen, Inc. - Biography
The therapeutic development process often involves evaluation of several key attributes, such as potency, safety, PK/PD, molecule manufacturability and immunogenicity. Since bio-therapeutics may elicit an immune response when administered in animals and humans, applying a quality by design immunogenicity assessment strategy during early therapeutic optimization can minimize immunogenicity associated risks. This study summarizes data generated using in silico, in vitro and in vivo immunogenicity related analytical tools utilized to support therapeutic development.
Read the speaker interview CHI conducted with Dr. Jawa titled "What do You Regard as the Greatest Challenges in Immunogenicity Today?"
9:05 In vitro Prediction Technologies for Immunogenicity Assessment
Valerie Quarmby, Ph.D., Director and Principal Scientist, BioAnalytical Sciences, Genentech, Inc. - Biography
This talk will discuss unwanted immune responses to biologics, and review what immunogenicity risk assessment tools, technologies and data sets may be deployed to enable informed decision making during biotherapeutics product and process development. The talk will also discuss recent data from selected in vitro models and highlight “gaps” where there may be opportunities to even further develop/refine such tools and technologies.
9:35 Case Studies Showing How T Cell Epitope Analysis Can be Used as a Basis for the Design of the Clinical Immunogenicity Program
Timothy Hickling, Ph.D., Associate Research Fellow, PDM Immunogenicity Sciences, Pfizer, Inc. - Biography
Several tools exist for characterizing T cell epitopes, from in silico prediction, through in vitro characterization to direct in vivo validation. The helper T cells themselves are crucial in driving immunoglobulin switching and strong anti-drug antibody responses, leading to the possibility that the quantification of T cell epitopes could relate directly to the incidence of clinical immunogenicity. A selection of case studies relating T cell epitope assessments and clinical incidence of ADA will be presented. Understanding of clinically relevant T cell responses, through clinical quantification and HLA typing, could direct re-engineering of novel biotherapeutics to reduce immunogenicity risk.
10:05 Advances in Tools for Managing Immunogenicity Risk: How an Integrated Approach Can Help
Nikolai Schwabe, Ph.D., CEO, ProImmune Limited
ProImmune has developed a comprehensive suite of in vitro assays to characterize immune responses against biological drugs. Assays that characterize DC, T cell and B cell responses can be combined to provide a comprehensive picture of the antigenicity of a therapeutic protein. The data from these assays enable well-informed design or selection of lead candidates, and can give a better understanding of the mechanisms underlying observed immunogenicity
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
IMMUNE TOLERANCE APPROACHES/REDUCING IMMUNOGENICITY
11:40 Reducing the Immunogenicity of Recombinant Immunotoxins by Identifying and Removing T Cell Epitopes
Mazor Ronit, M.Sc., Laboratory of Ira Pastan, Molecular Biology, NIH - Biography
Moxetumomab pasudotox and SS1P are immunotoxins that have been developed in our lab to treat cancer. In order to identify and eliminate T-cell epitopes, we used an in vitro expansion step which specifically expands T-cell populations that are reactive to naturally processed peptide, followed by ELISpot. This strategy had a 100% response rate which correlates with the immunogenicity response rate of patients with solid tumors that have been treated with the immunotoxin. We identified one highly-reactive and immunodominant epitope that stood out among multiple subdominant epitopes and constructed mutant RITs that retained sufficient protein expression, stability, activity, and had reduced T-cell immunogenicity.
12:10-1:00 pm In-Depth Breakout Discussions - Detailed Agenda
Table 1: Product-Related Factors that Contribute to Immunogenicity
Moderator: Wim Jiskoot, Ph.D., Professor, Division of Drug Delivery Technology, Leiden University
Table 2: To what Extent can Immunogenicity Prediction Affect the Clinical Strategy?
Moderator: Timothy Hickling, Ph.D., Associate Research Fellow, PDM Immunogenicity Sciences, Pfizer, Inc.
Table 3: Immune Tolerance Approaches
Moderator: Amy Rosenberg, M.D., Director, Therapeutic Proteins, CDER/FDA
Table 4: Prediction Technologies for Immunogenicity
Valerie Quarmby, Ph.D., Director and Principal Scientist, BioAnalytical Sciences, Genentech, Inc.
Table 5: To What Extent Can Non-Immunogenic Lead Candidates be Selected?
Moderator: Nikolai Schwabe, CEO, ProImmune
Table 6: How Predictive are the Methods to Analyze T cell Epitopes?
Moderator: Matthew Baker, Ph.D., CSO, Antitope Ltd.
1:00 Luncheon Presentation
(Opportunity available, please contact Tim McLucas, email@example.com) or Lunch on Your Own
2:00 Chairperson’s Remarks
Paul Chamberlain, NDA Advisory Board
2:05 Immune Tolerance Induction: Novel Approaches for Novel Clinical Indications
Amy S. Rosenberg, M.D., Director, Division of Therapeutic Proteins, CDER/FDA - Biography
The choice of the tolerance induction regimen must consider the following: the appropriate regimen for the level of risk posed by the immune response; and the rapidity with which treatment for the underlying disease must be initiated. Thus, the need for expedient commencement of therapy for the underlying disease may restrict tolerance protocols to those which are less specific and more hazardous as regards infectious risk. This seminar will explore these various considerations in tolerance induction approaches focusing on novel approaches and novel clinical indications.
2:35 Peptides that Act as T Regulators: Implications for Control of Immunogenicity and Application to Protein Therapeutics
Annie de Groot, Ph.D., Director, Institute for Immunology & Informatics, University of Rhode Island - Biography
Immune responses to protein therapeutics and contaminating host cell proteins (HCP) can diminish drug safety and efficacy. This presentation addresses the critical role of T cell immunogenicity in early events leading to anti-drug antibody production. Effector T cell responses enhance anti-drug antibodies (ADA) while Regulatory T cell responses can suppress them. Case studies of epitope modification and tolerance induction to reduce immunogenicity risk, as well as potential immunogenicity of HCP contaminants, will be presented.
3:05 Lipid Mediated Induction of Immunological Ignorance/Tolerance
Sathy Balu-Iyer, Ph.D., Associate Professor, Pharmaceutical Sciences, SUNY-University at Buffalo - Biography
Immunogenic responses against therapeutic proteins are a major clinical complication that greatly impact safety and efficacy of protein based therapies. The talk focuses on lipid mediated Induction of immunological tolerance/ignorance. The pre-clinical studies showed that immunization with protein- phosphatidylserine complex lead to hypo-responsiveness towards therapeutic protein and this hypo-responsiveness could be adoptively transferred to a recipient mouse. Based on this novel finding, a reverse vaccination strategy is proposed as clinical intervention to mitigate immunogenicity of therapeutic proteins.
3:35 PANEL DISCUSSION: Risk Assessment and Risk Management
Amy Rosenberg, M.D., Director, Therapeutic Proteins, CDER/FDA
Additional Panellists to be Announced
Timothy Hickling, Ph.D., Associate Research Fellow, PDM Immunogenicity Sciences, Pfizer, Inc.
- Management in the clinic of products with low and high risk of immunogenicity related adverse events
- Investigative approaches to consider when only a sub population 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
4:00 End of Conference
Day 1 | Day 2 | Combined Session | Download Brochure
Part One | Part Two