| Autor: |
Stephens, S., Emtage, S., Vetterlein, O., Chaplin, L., Bebbington, C., Nesbitt, A., Sopwith, M., Athwal, D., Novak, C., Bodmer, M. |
| Předmět: |
|
| Zdroj: |
Immunology; Aug95, Vol. 85 Issue 4, p668-674, 7p |
| Abstrakt: |
A murine antibody to human turnout necrosis factor-α (TNF-α) (CB0010) was complementarity-determining region (CDR)-grafted using human IgG4 heavy and K light chain constant regions. In cynomolgus monkeys, the grafted antibody (CDP571) was eliminated with a half-life of 40-90 hr, two to three times longer than CB0010, and immunogenicity was reduced by > 90%. Responses to the constant regions were almost entirely eliminated and responses to the CDR loops (antiidiotype) were lowered. CDP571 was given to 24 human volunteers in doses from 0.1 to 10.0 mg/ kg. It was well tolerated, with a half-life of approximately 13 days. Anti-CDP571 antibodies were low or undetectable at higher doses. At lower doses, anti-CDP571 peaked at 2 weeks and then declined. The response was primarily IgM (in contrast to the cynomolgus monkey, where by 5 weeks IgG predominated) and was against a conformational epitope comprising heavy and light chain CDR loops. No antibodies were detected against the γ4κ domains or frameworks. The response had little or no effect on CDPS71 binding to TNF-α or on plasma clearance. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
