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Structure-immunogenicity relationships of therapeutic proteins
Suzanne Hermeling1, Daan J A Crommelin, Huub Schellekens
1Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands. S.Hermeling@pharm.uu.nl
Pharmaceutical Research
|June 24, 2004
Summary
Therapeutic protein immunogenicity is increasing. Structural properties and degradation, like aggregation, significantly influence antibody formation, impacting drug efficacy and safety.
Area of Science:
- Biotechnology
- Immunology
- Protein Therapeutics
Background:
- Rising incidence of immunogenicity issues with increasing availability of recombinant human proteins.
- Antibodies against therapeutic proteins can cause loss of efficacy and neutralize endogenous proteins.
Purpose of the Study:
- To review literature on the relationship between therapeutic protein immunogenicity and structural properties.
- To discuss mechanisms of antibody induction and models for studying protein immunogenicity.
Main Methods:
- Literature review focusing on structure-immunogenicity relationships.
- Analysis of chemical structure (amino acid sequence, glycosylation, pegylation) effects.
- Evaluation of physical degradation (aggregation) and chemical decomposition (oxidation) impacts.
Main Results:
- Chemical structure significantly influences antibody formation incidence and levels.
- Protein degradation, particularly aggregation and oxidation, can enhance immune responses.
- Further investigation is needed on the immunogenicity impact of degradation products in formulations.
Conclusions:
- Therapeutic protein structure and degradation are critical factors in immunogenicity.
- Understanding these relationships is key to developing safer and more effective protein therapeutics.
- Future studies using degradation products in animal models may clarify structure-immunogenicity links.