Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins

Biologics have emerged as a powerful and diverse class of molecular and cell-based therapies that are capable of replacing enzymes, editing genomes, targeting tumors, and more. As this complex array of tools arises a distinct set of challenges is rarely encountered in the development of small molecu...

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Published in:Journal of immunology research 2016-01, Vol.2016 (2016), p.1-9
Main Authors: Theil, Frank-Peter, Epstein, Alan L., Frutoz, Kimberley, Jaw, Stacey, Manoli, Hugh, Smith, Alison, Khawli, Leslie A.
Format: Article
Language:English
Subjects:
Animals
Biological products
Biological Products - adverse effects
Biological Products - immunology
Biological Products - pharmacokinetics
Biological Products - pharmacology
Computer Simulation
Disease
Disease Management
Drug dosages
Enzymes
Genetic engineering
Humans
Immunoassay
Immunoglobulins
Immunologic Factors - immunology
Immunologic Factors - pharmacology
Immunology
Immunomodulation
Models, Biological
Models, Immunological
Patients
Pharmaceutical industry
Protein Engineering
Proteins - adverse effects
Proteins - immunology
Proteins - pharmacokinetics
Proteins - pharmacology
Review
Risk Factors
Treatment Outcome
Tumor necrosis factor-TNF
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description Biologics have emerged as a powerful and diverse class of molecular and cell-based therapies that are capable of replacing enzymes, editing genomes, targeting tumors, and more. As this complex array of tools arises a distinct set of challenges is rarely encountered in the development of small molecule therapies. Biotherapeutics tend to be big, bulky, polar molecules comprised of protein and/or nucleic acids. Compared to their small molecule counterparts, they are fragile, labile, and heterogeneous. Their biodistribution is often limited by hydrophobic barriers which often restrict their administration to either intravenous or subcutaneous entry routes. Additionally, their potential for immunogenicity has proven to be a challenge to developing safe and reliably efficacious drugs. Our discussion will emphasize immunogenicity in the context of therapeutic proteins, a well-known class of biologics. We set out to describe what is known and unknown about the mechanisms underlying the interplay between antigenicity and immune response and their effect on the safety, efficacy, pharmacokinetics, and pharmacodynamics of these therapeutic agents.
doi_str_mv 10.1155/2016/2342187
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subjects Animals
Biological products
Biological Products - adverse effects
Biological Products - immunology
Biological Products - pharmacokinetics
Biological Products - pharmacology
Computer Simulation
Disease
Disease Management
Drug dosages
Enzymes
Genetic engineering
Humans
Immunoassay
Immunoglobulins
Immunologic Factors - immunology
Immunologic Factors - pharmacology
Immunology
Immunomodulation
Models, Biological
Models, Immunological
Patients
Pharmaceutical industry
Protein Engineering
Proteins - adverse effects
Proteins - immunology
Proteins - pharmacokinetics
Proteins - pharmacology
Review
Risk Factors
Treatment Outcome
Tumor necrosis factor-TNF
title Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins
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