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Highly Frequent Anti-Idiotype Antibody in Cynomolgus Monkeys Developed Against Mouse-Derived Regions of anti-Fas Antibody Humanized by Complementarity Determining Region Grafting

Highly Frequent Anti-Idiotype Antibody in Cynomolgus Monkeys Developed Against Mouse-Derived Regions of anti-Fas Antibody Humanized by Complementarity Determining Region Grafting

M Saito-Yabe, Y Yoshigae, W Takasaki, A Kurihara, T Ikeda, O Okazaki

Br J Pharmacol. 2009 Sep;158(2):548-57.

PMID: 19645714

Abstract:

Background and purpose:
We investigated the immunogenicity of a humanized anti-human Fas monoclonal antibody, R-125224, in cynomolgus monkeys to estimate its efficacy, as well as its toxicity in clinical situations.
Experimental approach:
R-125224 was intravenously administered to cynomolgus monkeys at single doses of 0.4, 1.2, 6 and 30 mg kg(-1), and the plasma concentrations of R-125224 and anti-R-125224 antibody (ARA) were measured. We conducted a competitive enzyme-linked immunosorbent assay to determine which part of R-125224 was recognized by ARA. We also examined the retention of radioactivity in mononuclear cells and granulocytes after the injection of [(125)I]-R-125224 to a collagen-induced arthritis monkey model.
Key results:
After i.v. administration of R-125224, the elimination of the plasma R-125224 concentrations was accelerated at around 10 days post-dose, and 10 of 12 monkeys were ARA positive. From an epitope analysis of ARA, the ARA produced in monkeys recognized the mouse-derived regions located in complementarity determining regions, but could not recognize the human IgG. After the injection of [(125)I]-R-125224 to a collagen-induced arthritis monkey model, a significantly longer retention of the radioactivity in mononuclear cells compared to granulocytes was observed.
Conclusions and implications:
In monkeys, the development of antibodies against R-125224 is rapid and highly frequent. Our hypothesis is that this highly frequent development of ARA might be due to the binding of R-125224 to immune cells, and its circulation in monkey blood might contribute to an increase in its chances of being recognized as an immunogen.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42412906	Monoclonal Anti-FAS antibody produced in mouse			Price

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