Immunogenicity of aggregates of recombinant human growth hormone in mouse models.
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.
Fradkin
Amber Haynes
AH
University of Colorado at Boulder, Engineering Drive, Boulder, Colorado 80309, USA.
Carpenter
John F
JF
Randolph
Theodore W
TW
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
D011994:Recombinant Proteins; D019382:Human Growth Hormone