The mechanism of tumor allograft survival induced by CP-17,193

CP-17,193 was examined in vivo for its immunosuppressive effects and for its promotion of E1(4) tumor allograft survival. At a dose of 10 mg/kg p.o., it was shown to suppress the development of both antibody-dependent and cellular cytotoxicity for E1(4) cells. After cessation of drug treatment, and in contrast to what is observed with cyclophosphamide, the humoral immune response was promptly restored. The restoration of cellular cytotoxicity followed a more protracted course, and the tumor allograft was not rejected by day 24. Three possible mechanisms of immunosuppression were examined. CP-17,193 was shown to inhibit the formation of IL-2 sensitive blasts. However, it had no effect on T cell proliferation using performed blasts in the presence of added IL-2, and it did inhibit IL-2 production. Its immunosuppressive effects might therefore be explained by an inhibition of some initial step of lymphocyte activation which interferes with the T lymphocyte's ability to progress on to cell division and IL-2 production after stimulation.