PROLONGED ACTION OF A CHIMERIC INTERLEUKIN-2 RECEPTOR (CD25) MONOCLONAL-ANTIBODY USED IN CADAVERIC RENAL-TRANSPLANTATION

A high affinity chimeric CD25 mAb (chRFT5: SDZ CHI 621) blocking inter leukin-2 binding to the interleukin-2 receptor alpha-chain was evaluat ed in a phase I/II study in human renal cadaveric transplantation. The chRFT5 was well tolerated with no immediate adverse effects during 6 spaced infusions (from before transplantation to day 24) in 24 patient s escalating from 2.5- to 25-mg dosages, The chRFT5 had a long termina l half-life with a mean of 13.1 days, There was good correlation betwe en the detection of chRFT5 in the serum by radioimmunoassay, the coati ng and suppression of CD25 on T cells, and antibody activity in patien t serum samples. The chRFT5 activity persisted in vivo for up to 120 d ays. No antibody response to the chRFT5 was detected in any of the pat ients, even though two patients who required treatment with antithymoc yte globulin or OKT3 developed xenogeneic antiglobulin responses while chRFT5 was still present in vivo. There was a 33% incidence of reject ion and the first rejection episode always occurred during chRFT5 ther apy. Patients who did not reject during therapy did not reject during the first year following transplantation. Equal numbers of patients re ceived dual and triple immunosuppressive therapy together with chRFT5. Posttransplant lymphoproliferative disorder developed in 2 patients, both on triple therapy, at 9 months after transplantation. The disorde r did not develop in any patient receiving dual therapy, and no furthe r cases have been observed to a minimum of 2 years' follow-up. No othe r viral, fungal, or bacterial infectious complications were prevalent in patients treated with chRFT5.