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  • Title: The novel calcineurin inhibitor ISA247: a more potent immunosuppressant than cyclosporine in vitro.
    Author: Bîrsan T, Dambrin C, Freitag DG, Yatscoff RW, Morris RE.
    Journal: Transpl Int; 2005 May; 17(12):767-71. PubMed ID: 15827754.
    Abstract:
    ISA247 is a novel cyclosporine analog. In this study we compare, in vitro, the effects of ISA247 on immune function with those of cyclosporine. Whole blood from cynomolgus monkeys (n = 5) was incubated with different concentrations of ISA247 or cyclosporine and stimulated with different mitogens in culture medium. Lymphocyte proliferation was assessed by [3H]-TdR incorporation assay and by flow cytometry. Flow cytometry was also used to assess production of intracellular cytokines by T cells and expression of T cell activation surface antigens. The concentration of drug necessary to attain 50% of the maximum effect (EC50) was subsequently calculated. EC50 values for ISA247 were lower than for cyclosporine, and the differences were statistically significant for lymphocyte proliferation, T cell cytokine production, and expression of all T cell activation surface antigens but one. We conclude that ISA247 suppresses diverse immune functions more potently than cyclosporine in vitro.
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