A phase‐i study of repeated therapy with radiolabelled antibody to carcinoembryonic antigen using intermittent or continuous administration of cyclosporin a to suppress the immune response

Abstract

The anti‐mouse antibody response was examined in patients receiving repeated i.v. therapy with radiolabeled mouse monoclonal antibody (MAb) to carcinoembryonic antigen (CEA): ¹³¹I anti‐CEA was given approximately every 2 weeks with cyclosporin A, to suppress the anti‐mouse antibody 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 of ml anti‐CEA. The nadir platelet count was related to the half‐life of ¹³¹I anti‐CEA in blood. Thrombocytopenia limited the amount of ¹³¹I 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 radiolabeled antibody.