title: Immunogenicity of aggregates of recombinant human growth hormone in mouse models.
abstract: Aggregation of recombinant therapeutic protein products is a concern due to their potential to induce immune responses. We examined the immunogenicity of protein aggregates in commercial formulations of recombinant human growth hormone produced by freeze-thawing or agitation, two stresses commonly encountered during manufacturing, shipping and handling of therapeutic protein products. In addition, we subjected each preparation to high-pressure treatment to reduce the size and concentration of aggregates present in the samples. Aggregates existing in a commercial formulation, as well as aggregates induced by freeze-thawing and agitation stresses enhanced immunogenicity in one or more mouse models. The use of high-pressure treatment to reduce size and concentrations of aggregates within recombinant human growth hormone formulations reduced their overall immunogenicity in agreement with the "immunon" hypothesis.
authors: University of Colorado at Boulder, Engineering Drive, Boulder, Colorado 80309, USA.
authors: Amber Haynes
authors: AH
authors: Fradkin
authors: John F
authors: JF
authors: Carpenter
authors: Theodore W
authors: TW
authors: Randolph
mesh_terms: D000818:Animals; D000917:Antibody Formation; D011232:Chemical Precipitation; D005260:Female; D005612:Freeze Drying; D019382:Human Growth Hormone / Q000276:immunology* / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D011247:Pregnancy; D011312:Pressure; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D012995:Solubility
chemical_list: D011994:Recombinant Proteins; D019382:Human Growth Hormone