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by Bonnie Rup

Bonita RupIn March, I attended the Third Annual Meeting of the ABIRISK consortium, a project of the Innovative Medicines Initiative (IMI). ABIRISK stands for “anti-biopharmaceutical immunogenicity: prediction and analysis of clinical relevance to reduce the RISK.“ It was really exciting to see the progress being made by this large network of clinicians, biologists, immunologists, and biostatisticians. These experts are joining together to analyze the clinical relevance of anti-drug antibodies (ADAs), to understand the underlying mechanisms of immunogenicity, and to improve the prediction approaches, all with the goal of minimizing this risk that has confounded the development and clinical management of many biopharmaceutical therapies.

For example, the products being studied by ABIRISK include factor VIII, interferons, and TNF antagonists, all of which induce ADAs in subsets of patients, a process that can result in loss of efficacy or safety consequences such as hypersensitivity reactions or autoimmune events. The potential for these negative consequences requires increased monitoring and, in some cases, switching to alternative therapeutics, in order to ensure that patients are receiving continued clinical benefit and minimal risk. Yet there are currently significant gaps in our understanding of the underlying factors that result in immunogenicity and in availability of reliable methods to predict the occurrence of immunogenicity. ABIRISK aspires to address these gaps in order to minimize this risk in the future.

ABIRISK is organized into 5 “work packages”, the third of which (WP3) is dedicated entirely to technologies of immunogenicity prediction. The main objectives of WP3 are to evaluate the relevance of existing approaches (e.g., in silico T cell epitope prediction software programs and in vitro T lymphocyte activation assays), to develop new predictive assays, and to address the specific effects of aggregates on immunogenicity. In addition to evaluating different versions the in silico and in vitro assays, WP3 is also evaluating advanced methods to identify immune epitopes and humanized mouse and artificial lymph node models. Results will be compared with measurements of ADAs and cellular immune responses generated by other WPs.

To learn more about recent progress being made in ABIRISK WP3 and participate in an exciting discussion about the potential of this work, please attend the Recent Progress from the ABIRISK Consortium: Technologies of Immunogenicity Prediction hot topic session on May 20 at the upcoming AAPS National Biotechnology Conference in San Diego. You can also learn more about the progress being made in the ABIRISK Project and read highlights of its annual meeting in the March 2014 Newsletter; or to learn more about ABIRISK or the IMI you can also visit the ABIRISK and IMI sites.

Bonita (Bonnie) Rup, Ph.D., is a research fellow in the Pharmacokinetics, Dynamics and Metabolism-New Biological Entity (PDM-NBE) organization at Pfizer’s Andover, Mass., site, where she leads the PDM-NBE Immunogenicity Discipline, which applies immunogenicity expertise and state of the art immunogenicity prediction tools to inform immunogenicity risk assessment for the R&D portfolio.