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
✍ Scribed by J. A. Ledermann; R. H. J. Begent; C. Massof; A. M. B. Kelly; T. Adam; K. D. Bagshawe
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- French
- Weight
- 627 KB
- Volume
- 47
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
The anti-mouse antibody response was examined in patients receiving repeated i.v. therapy with radiolabelled mouse monoclonal antibody (MAb) to carcinoembryonic antigen (CEA): l 3 I l 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 l3Il anti-CEA. The nadir platelet count was related to the half-life of l3Il anti-CEA in blood. Thrombocytopenia limited the amount of '"'I 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.