OKT3: First-dose safety and success

Abstract

Orthoclone OKT3 is a murine monoclonal antibody that has been shown to be effective in reversing acute rejection episodes. In a randomized, multicenter trial, Orthoclone OKT3 reversed 94% of acute rejection episodes; conventional treatments reversed only 75%. However, early trials also disclosed some limitations of OKT3 therapy, such as a severe febrile or bronchospastic response following the initial injection, recurrent rejection episodes after discontinuation of OKT3 administration, or the host's production of antibodies to the murine immunoglobulin. In later experiments modifications and precautions applied to the therapeutic helped to control first-dose reactions and decrease antibody production from 86 to 39%. Furthermore, recurrent rejection episodes occurring after discontinuation of OKT3 therapy in azathioprine-prednisone-treated patients have been shown to be reversible in most cases: a 75% rate of long-term (14- to 26-month) allograft survival has been achieved in these patients. More recently, OKT3 treatment administered to allograft recipients receiving cyclosporin has been shown to benefit 15-20% of patients when administered at the time of rejection. This combination approach not only reverses the rejection, but also seems to significantly reduce the incidence of subsequent rejection episodes. OKT3 has raised clinical immunosuppressive specificity to a higher level than previous therapies such as steroids or cytotoxic agents. OKT3 appears to be safe and effective therapy for patients receiving cyclosporin or azathioprine-prednisone therapy. Despite certain unresolved limitations, it may be a successful prototype for future, even more highly specific, immunosuppressive protocols.