Scientific Publications by FDA Staff

Trends Biotechnol 2018 Oct;36(10):1068-84

Evaluating and mitigating the immunogenicity of therapeutic proteins.

Sauna ZE, Lagasse D, Pedras-Vasconcelos J, Golding B, Rosenberg AS

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.