Immunogenicity of therapeutic protein aggregates

Medicina Fluminensis

Mijić, Ivana²  Marinc, Sabina¹  Cindrić, Mario² 

[1] Pliva Hrvatska d.d., HrvatskaPliva Hrvatska d.d., Croatia;Insti tut “Ruđer Bošković”, Zavod za molekularnu medicinu, Laboratorij za sistemsku biomedicinu,, Zagreb, HrvatskaDivision of molecular medicine, Laboratory for systemic biomedicine, Rudjer Boskovic Institute, Zagreb, Croatia

关键词: analytical methods;    antigen structure;    immunogenicity;    protein aggregation;   

DOI  :  

学科分类：医学（综合）

来源: Medicina Fluminensis

【 摘 要 】

Aggregati on is a signifi cant problem in pharmaceuti cal administrati on of proteins,
since it can end up with several detrimental eff ects including the loss of acti vity, altered
half-life in bloodstream, and increased immunogenicity. Aggregati on provoking factors
may be structural characteristi cs of protein (internal factors) or environmental conditi ons
(external factors). Despite the fact that protein aggregati on represents one of the most possible
factor that lead to immunogenicity toward therapeuti c proteins, the mechanism of aggregates
induced immunogenicity is not yet understood. However, it is known that multi -
meric anti gen presentati on and anti gen conformati ons changes have the key role in
immunogenecity of therapeuti c proteins aggregates.
Because of severe pharmaceuti cal consequences of protein aggregati on, the methods aimed
to assess the degree of aggregati on are required for the development of a safe and effi cacious
protein drug product. Quanti fi cati on of aggregati on is oft en diffi cult and compounded by multi
ple forms in which the aggregates may be found. A number of methods have been successfully
employed to monitor and quanti fy protein aggregati on. These methods include the separati
on techniques like size-exclusion chromatography, gel electrophoresis, fi eld fl ow
fracti onati on and analyti cal ultracentrifugati on, and detecti on spectroscopic techniques like
UV/VIS, fl uorescence detecti on, dynamic light scatt ering and multi -angle laser light scatt ering,

【 授权许可】

Unknown