Immunogenicity to therapeutic proteins

Impact on PK/PD and efficacy

Narendra Chirmule, Vibha Jawa, Bernd Meibohm

Research output: Contribution to journalReview article

135 Citations (Scopus)

Abstract

The development of therapeutic proteins requires the understanding of the relationship between the dose, exposure, efficacy, and toxicity of these molecules. Several intrinsic and extrinsic factors contribute to the challenges for measuring therapeutic proteins in a precise and accurate manner. In addition, induction of an immune response to therapeutic protein results in additional complexities in the analysis of the pharmacokinetic profile, toxicity, safety, and efficacy of this class of molecules. Assessment of immunogenicity of therapeutic proteins is a required aspect of regulatory filings for a licensing application and for the safe and efficacious use of these compounds. A systematic strategy and well-defined criteria for measuring anti-drug antibodies (ADA) have been established, to a large extent, through coordinated efforts. These recommendations are based on risk assessment and include the determination of ADA content (concentration/titer), affinity, immunoglobulin isotype/subtype, and neutralization capacity. This manuscript reviews the requirements necessary for understanding the nature of an ADA response in order to discern the impact of immunogenicity on pharmacokinetics/pharmacodynamics and efficacy.

Original languageEnglish (US)
Pages (from-to)296-302
Number of pages7
JournalAAPS Journal
Volume14
Issue number2
DOIs
StatePublished - Jun 1 2012

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Anti-Idiotypic Antibodies
Proteins
Pharmacokinetics
Pharmaceutical Preparations
Intrinsic Factor
Immunoglobulin Isotypes
Licensure
Therapeutics
Systems Analysis
Antibody Formation
Safety

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Immunogenicity to therapeutic proteins : Impact on PK/PD and efficacy. / Chirmule, Narendra; Jawa, Vibha; Meibohm, Bernd.

In: AAPS Journal, Vol. 14, No. 2, 01.06.2012, p. 296-302.

Research output: Contribution to journalReview article

Chirmule, Narendra ; Jawa, Vibha ; Meibohm, Bernd. / Immunogenicity to therapeutic proteins : Impact on PK/PD and efficacy. In: AAPS Journal. 2012 ; Vol. 14, No. 2. pp. 296-302.
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