Autor: |
Zwickl CM; Toxicology Division, Lilly Research Laboratories, Eli Lilly and Company, Greenfield, Indiana 46140., Cocke KS, Tamura RN, Holzhausen LM, Brophy GT, Bick PH, Wierda D |
Jazyk: |
angličtina |
Zdroj: |
Fundamental and applied toxicology : official journal of the Society of Toxicology [Fundam Appl Toxicol] 1991 Feb; Vol. 16 (2), pp. 275-87. |
DOI: |
10.1016/0272-0590(91)90112-h |
Abstrakt: |
The relative concentrations of antibodies produced in monkeys against three forms of human growth hormone (hGH) were determined using an antigen-specific avidin/biotin ELISA assay. Monkeys were treated in two separate 90-day studies with recombinant methionyl-hGH (met-hGH) and pituitary-derived hGH (pit-hGH) (Study 1) and recombinant natural sequence hGH (Study 2). The lowest dose was equal to the expected therapeutic dose of 0.1 IU/kg. Sixty-nine percent of monkeys treated with pit-hGH and 81% of those treated with met-hGH developed detectable anti-hGH responses. The magnitudes of the responses exhibited wide animal to animal variability, were not markedly related to dose or sex, and were lower than levels obtained in monkeys immunized with hGH in Freund's adjuvant. In contrast, the incidence of antibody responses in monkeys treated with natural sequence hGH was lower (23% in one experiment and 5% in a replicate experiment) and took longer to develop. Antibody concentrations were lower, on average, than in those animals treated with met- or pit-hGH. These results are in accord with those observed clinically, thus supporting the use of the monkey model to predict the relative immunogenicity of some proteins in humans. |
Databáze: |
MEDLINE |
Externí odkaz: |
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