Immunogenicity of protein therapeutics

Protein therapeutics, such as monoclonal antibodies, enzymes and toxins, hold significant promise for improving human health. However, repeated administration of protein therapeutics, whether natural or recombinant, often leads to the induction of undesirable anti-drug antibodies (ADAs), which inter...

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Published in	Trends in immunology Vol. 28; no. 11; pp. 482 - 490
Main Authors	De Groot, Anne S., Scott, David W.
Format	Journal Article
Language	English
Published	England Elsevier Ltd 01.11.2007 Elsevier Limited
Subjects	Allergy and Immunology Animals Antibodies - immunology Antibodies, Monoclonal - immunology Antibodies, Monoclonal - therapeutic use B-Lymphocytes - immunology Cross Reactions Drug dosages Histocompatibility Antigens Class II - immunology Humans Immune system Immune Tolerance Immunoassay - methods Ligands Lymphocyte Activation Lymphocytes Majority stockholders Medical research Protein Engineering - methods Proteins Proteins - immunology Proteins - therapeutic use Recombinant Proteins - immunology Recombinant Proteins - therapeutic use Regulation Studies T-Lymphocytes - immunology Vaccines
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Abstract	Protein therapeutics, such as monoclonal antibodies, enzymes and toxins, hold significant promise for improving human health. However, repeated administration of protein therapeutics, whether natural or recombinant, often leads to the induction of undesirable anti-drug antibodies (ADAs), which interfere with or neutralize the effect of the drug. Although an immune response to foreign proteins can be expected and is well understood, the basis for the development of responses to therapeutic autologous proteins is the subject of some debate. Inflammatory components of the drug delivery vehicle, T cell responses, T and B cell epitopes in the protein drug, and the associated B cell response are all targets for interventions aimed at reducing ADA responses. Here, we review some theories put forward to explain the immunogenicity of therapeutic proteins and describe some emerging protein-engineering approaches that might prevent the development of anti-drug antibodies.
AbstractList	Protein therapeutics, such as monoclonal antibodies, enzymes and toxins, hold significant promise for improving human health. However, repeated administration of protein therapeutics, whether natural or recombinant, often leads to the induction of undesirable anti-drug antibodies (ADAs), which interfere with or neutralize the effect of the drug. Although an immune response to foreign proteins can be expected and is well understood, the basis for the development of responses to therapeutic autologous proteins is the subject of some debate. Inflammatory components of the drug delivery vehicle, T cell responses, T and B cell epitopes in the protein drug, and the associated B cell response are all targets for interventions aimed at reducing ADA responses. Here, we review some theories put forward to explain the immunogenicity of therapeutic proteins and describe some emerging protein-engineering approaches that might prevent the development of anti-drug antibodies. Protein therapeutics, such as monoclonal antibodies, enzymes and toxins, hold significant promise for improving human health. However, repeated administration of protein therapeutics, whether natural or recombinant, often leads to the induction of undesirable anti-drug antibodies (ADAs), which interfere with or neutralize the effect of the drug. Although an immune response to foreign proteins can be expected and is well understood, the basis for the development of responses to therapeutic autologous proteins is the subject of some debate. Inflammatory components of the drug delivery vehicle, T cell responses, T and B cell epitopes in the protein drug, and the associated B cell response are all targets for interventions aimed at reducing ADA responses. Here, we review some theories put forward to explain the immunogenicity of therapeutic proteins and describe some emerging protein-engineering approaches that might prevent the development of anti-drug antibodies.Protein therapeutics, such as monoclonal antibodies, enzymes and toxins, hold significant promise for improving human health. However, repeated administration of protein therapeutics, whether natural or recombinant, often leads to the induction of undesirable anti-drug antibodies (ADAs), which interfere with or neutralize the effect of the drug. Although an immune response to foreign proteins can be expected and is well understood, the basis for the development of responses to therapeutic autologous proteins is the subject of some debate. Inflammatory components of the drug delivery vehicle, T cell responses, T and B cell epitopes in the protein drug, and the associated B cell response are all targets for interventions aimed at reducing ADA responses. Here, we review some theories put forward to explain the immunogenicity of therapeutic proteins and describe some emerging protein-engineering approaches that might prevent the development of anti-drug antibodies.
Author	Scott, David W. De Groot, Anne S.
Author_xml	– sequence: 1 givenname: Anne S. surname: De Groot fullname: De Groot, Anne S. email: annied@brown.edu, annied@epivax.com organization: EpiVax, Inc., 146 Clifford Street, Providence, RI 02903, USA – sequence: 2 givenname: David W. surname: Scott fullname: Scott, David W. organization: Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/17964218$$D View this record in MEDLINE/PubMed
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Snippet	Protein therapeutics, such as monoclonal antibodies, enzymes and toxins, hold significant promise for improving human health. However, repeated administration...
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SubjectTerms	Allergy and Immunology Animals Antibodies - immunology Antibodies, Monoclonal - immunology Antibodies, Monoclonal - therapeutic use B-Lymphocytes - immunology Cross Reactions Drug dosages Histocompatibility Antigens Class II - immunology Humans Immune system Immune Tolerance Immunoassay - methods Ligands Lymphocyte Activation Lymphocytes Majority stockholders Medical research Protein Engineering - methods Proteins Proteins - immunology Proteins - therapeutic use Recombinant Proteins - immunology Recombinant Proteins - therapeutic use Regulation Studies T-Lymphocytes - immunology Vaccines
Title	Immunogenicity of protein therapeutics
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