Evaluating and Mitigating the Immunogenicity of Therapeutic Proteins. Issue 10 (October 2018)

• Record Type: Journal Article
• Authors: Sauna, Zuben E.; Lagassé, Daniel; Pedras-Vasconcelos, Joao; Golding, Basil; Rosenberg, Amy S.
• Is Part Of: Trends in biotechnology. Volume 36:Issue 10(2018)
• Page Start: 1068
• Page End: 1084
• Publication Date: 2018-10
• Subjects: drug development -- therapeutic proteins -- immunogenicity -- anti-drug antibodies; Biotechnology -- Periodicals; Biochemical engineering -- Periodicals; Genetic engineering -- Periodicals; Industrial microbiology -- Periodicals; 660.605
• DOI: 10.1016/j.tibtech.2018.05.008
• Languages: English
• ISSNs: 0167-7799

Abstract

Abstract : Therapeutic proteins provide interventions for some of the most complex and intractable diseases and are an essential part of modern medicine. Immunogenicity is the development of immune responses, usually measured by antibodies, to therapeutic proteins. These responses can adversely affect the safety and efficacy of the therapeutic agent and may have the following consequences: neutralization of a life-saving biotherapeutic, crossreactivity to non-redundant endogenous proteins, and hypersensitivity responses. These concerns have been underscored by the discontinuation of development of several drugs in recent years owing to immunogenicity issues. We review here recent progress in technological approaches that are useful for the clinical and non-clinical risk assessment of immunogenicity as well as mitigation strategies including deimmunizing protein molecules and inducing immune tolerance to the therapeutic protein. Highlights: Immunogenicity compromises the safety and/or efficacy of therapeutic proteins, is a priority for regulatory agencies, and adds to the risks and costs associated with drug development. In the clinical setting, the risks and consequences of anti-drug antibodies translate into complex decision-making, and reliable immunogenicity testing strategies are therefore needed to inform clinical decisions. A multitude of non-clinical approaches (computational, in vitro, ex vivo, and animal models) are currently used to assess immunogenicity risk. Newly emerging technologies are expected to contribute to the rapid advancement of non-clinical assessments and have the potential to reduce the burden of immunogenicity. Novel strategies applied to protein therapeutic deimmunization or immune tolerance induction have the potential to reduce the incidence of immunogenicity and aid in better clinical management.