T-cell dependent immunogenicity of protein therapeutics Preclinical assessment and mitigation

T-cell dependent immunogenicity of protein therapeutics : Preclinical assessment and mitigation

© 2013. Published by Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 149(2013), 3 vom: 14. Dez., Seite 534-55
1. Verfasser: Jawa, Vibha (VerfasserIn)
Weitere Verfasser: Cousens, Leslie P, Awwad, Michel, Wakshull, Eric, Kropshofer, Harald, De Groot, Anne S
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2013
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Review 50% inhibitory concentration ADA ALN APC CFSE Cell-mediated immunity ELISA ELISpot mehr... FPX FVIII HLA IC(50) IEDB Immune Epitope Database Analysis Resource Immunogenicity; MHC ORG PBMC Quality-by-Design; SFC T T cell receptor T cell; T-cell dependent, thymus dependent T-cell independent TCR Td Ti Treg aTreg adaptive regulatory T cells anti-drug antibodies antigen-presenting cells artificial lymph node carboxyfluorescein succinimidyl ester enzyme-linked immunosorbent assay enzyme-linked immunosorbent spot-forming factor VIII human leukocyte antigen iTreg induced regulatory T cells major histocompatibility complex nTregs natural regulatory T cells peripheral blood mononuclear cells recombinant Fc fusion protein regulatory T cells spot-forming cells thymus unmodified original epitopes Antibodies, Monoclonal Biological Products Biomarkers, Pharmacological Cytokines Intercellular Signaling Peptides and Proteins Recombinant Proteins
Beschreibung
Zusammenfassung:© 2013. Published by Elsevier Inc. All rights reserved.
Protein therapeutics hold a prominent and rapidly expanding place among medicinal products. Purified blood products, recombinant cytokines, growth factors, enzyme replacement factors, monoclonal antibodies, fusion proteins, and chimeric fusion proteins are all examples of therapeutic proteins that have been developed in the past few decades and approved for use in the treatment of human disease. Despite early belief that the fully human nature of these proteins would represent a significant advantage, adverse effects associated with immune responses to some biologic therapies have become a topic of some concern. As a result, drug developers are devising strategies to assess immune responses to protein therapeutics during both the preclinical and the clinical phases of development. While there are many factors that contribute to protein immunogenicity, T cell- (thymus-) dependent (Td) responses appear to play a critical role in the development of antibody responses to biologic therapeutics. A range of methodologies to predict and measure Td immune responses to protein drugs has been developed. This review will focus on the Td contribution to immunogenicity, summarizing current approaches for the prediction and measurement of T cell-dependent immune responses to protein biologics, discussing the advantages and limitations of these technologies, and suggesting a practical approach for assessing and mitigating Td immunogenicity
Beschreibung:Date Completed 30.12.2013
Date Revised 03.12.2013
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2013.09.006