Prophylactic use of OKT3 monoclonal antibody in cadaver kidney recipients. Utilization of OKT3 as the sole immunosuppressive agent.
We describe the first clinical trial of OKT3, a monoclonal anti-T-cell antibody, for prevention of kidney transplant rejection. 13 patients receiving a first cadaveric kidney transplant were randomly assigned to conventional treatment with azathioprine and high-dose steroids (7 patients) or to treatment with daily injection of OKT3 alone (6 patients). The first OKT3 injection resulted in a dramatic decrease in T3+, T4+, and T8+ cells, while patients simultaneously experienced fever, chills, and diarrhea. These symptoms did not recur with subsequent injections. All six OKT3-treated patients had a rejection necessitating introduction of steroids 12.8 +/- 2.9 days after surgery. Rejection was related to appearance of anti-OKT3 antibodies leading to disappearance of detectable OKT3 in the serum. Modulating (T3-, T4+ or T3-, T8+) cells were observed in all patients but were functionally inactive. As no rejection was observed before day 9 posttransplant, despite the lack of additional immunosuppressive agents, we conclude that OKT3 is a powerful, well-tolerated immunosuppressive agent. However, it is highly immunogenic and anti-OKT3 antibodies lead to loss of clinical effectiveness in this protocol. The use of OKT3 alone for prevention of kidney graft rejection cannot be recommended until a method for reducing the effects of anti-OKT3 immunization is developed.
D000208:Acute Disease; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D002102:Cadaver; D004361:Drug Tolerance; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D011183:Postoperative Complications; D013601:T-Lymphocytes / Q000145:classification
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents