CAM - A NOVEL IMMUNOSUPPRESSIVE AGENT

This is an initial study of the immunosuppressive efficacy of CAM, a d erivative of mycophenolic acid, in a rat heart allograft model when th e major histocompatibility complex was fully incompatible, and its eff ect in improving heart allograft survival compared with mycophenolate mofetil (MMF, RS-61443). CAM or MMF was administered orally from day 1 following the allografting for 40 days. The median survival times (MS T) were 6 days in rats with no immunosuppressive drug (control group; n=6), 83 days with CAM 10 mg/kg (n=6), and > 100 days with both 20 mg/ kg (n=7), and 30 mg/kg (n=10). With MMF, in contrast, MST was 9, 17, 3 5, days with 10, 20, 30 mg/kg/day, respectively. Ah grafts in the CAM 30 mg/kg-treated group survived for more than 100 days after grafting, and, furthermore, CAM was also more effective than MMF in prolongatio n of the heart graft survival in rats at each dose. Rats with long-sur viving cardiac allografts (30 mg/kg; CAM) accepted skin grafts from th e donor-strain but rejected them from the third-party strain, suggesti ng that donor-specific tolerance was induced by CAM. In the tolerant r ats, proliferative response against donor-type alloantigen was not imp aired as compared with naive WKAH rats. In contrast, CML assay showed that T cells obtained from the rats bearing permanently accepted F344 heart grafts had less cytotoxic activity to the donor-type target, and the frequency of CTL precursor against donor-type alloantigen was als o reduced.