title: Therapeutic outcomes, assessments, risk factors and mitigation efforts of immunogenicity of therapeutic protein products.
abstract: Therapeutic protein products (TPPs) are of considerable value in the treatment of a variety of diseases, including cancer, hemophilia, and autoimmune diseases. The success of TPP mainly results from prolonged half-life, increased target specificity and decreased intrinsic toxicity compared with small molecule drugs. However, unwanted immune responses against TPP, such as generation of anti-drug antibody, can impact both drug efficacy and patient safety, which has led to requirements for increased monitoring in regulatory studies and clinical practice, termination of drug development, or even withdrawal of marketed products. We present an overview of current knowledge on immunogenicity of TPP and its impact on efficacy and safety. We also discuss methods for measurement and prediction of immunogenicity and review both product-related and patient-related risk factors that affect its development, and efforts that may be taken to mitigate it. Lastly, we discuss gaps in knowledge and technology and what is needed to fill these.
authors.affiliation: Pharmacokinetics, Dynamics and Metabolism-New Biological Entities, Pfizer, Andover, MA, United States.
authors.forename: Liusong
authors.initials: L
authors.lastname: Yin
authors.affiliation: Pharmacokinetics, Dynamics and Metabolism-New Biological Entities, Pfizer, Cambridge, MA, United States.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Chen
authors.affiliation: Pharmacokinetics, Dynamics and Metabolism-New Biological Entities, Pfizer, San Diego, CA, United States.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vicini
authors.affiliation: Pharmacokinetics, Dynamics and Metabolism-New Biological Entities, Pfizer, Andover, MA, United States.
authors.forename: Bonita
authors.initials: B
authors.lastname: Rup
authors.affiliation: Pharmacokinetics, Dynamics and Metabolism-New Biological Entities, Pfizer, Andover, MA, United States. Electronic address: Timothy.Hickling@Pfizer.com.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Hickling
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000917:Antibody Formation / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal
keywords: Efficacy; Immunogenicity; Prediction; Risk assessment; Safety; Therapeutic protein