A PHASE-I STUDY OF REPEATED THERAPY WITH RADIOLABELED ANTIBODY TO CARCINOEMBRYONIC ANTIGEN USING INTERMITTENT OR CONTINUOUS ADMINISTRATION OF CYCLOSPORINE-A TO SUPPRESS THE IMMUNE-RESPONSE

The anti-mouse antibody response was examined in patients receiving repeated i.v. therapy with radiolabelled mouse monoclonal antibody (MAb) to carcinoembryonic antigen (CEA): I-131 anti-CEA was given approximately every 2 weeks with cyclosporin A, to suppress the anti-mouse anti-body response. Two schedules of cyclosporin A-intermittent therapy for 6 days with each course of anti-CEA and continuous therapy-were compared. Suppression of the immune response in the intermittent high-dose (3 patients) and continuous low-dose groups (4 patients) was equivalent, but the latter regimen was less toxic. Repeated therapy led to the formation of small amounts of anti-mouse antibody, but provided that cyclosporin A was continued it did not prevent further therapy or lead to an increase in the rate of clearance of anti-CEA from blood. Without cyclosporin A no more than 2 courses of antibody therapy could be given. Patients received up to 4 doses I-131 anti-CEA. The nadir platelet count was related to the half-life of I-131 anti-CEA in blood. Thrombocytopenia limited the amount of I-131 anti-CEA that could be given and determined the interval between treatments. Effective suppression of the anti-antibody response is possible and this study has determined that myelosuppression is the principal obstacle to repeated therapy with radiolabelled antibody.