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 interleukin-2 binding to the interleukin-2 receptor alpha-chain was evaluated 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 patients escalating from 2.5- to 25-mg dosages. The chRFT5 had a long terminal half-life with a mean of 13.1 days. There was good correlation between the detection of chRFT5 in the serum by radioimmunoassay, the coating and suppression of CD25 on T cells, and antibody activity in patient serum samples. The chRFT5 activity persisted in vivo for up to 120 days. No antibody response to the chRFT5 was detected in any of the patients, even though two patients who required treatment with antithymocyte globulin or OKT3 developed xenogeneic antiglobulin responses while chRFT5 was still present in vivo. There was a 33% incidence of rejection and the first rejection episode always occurred during chRFT5 therapy. Patients who did not reject during therapy did not reject during the first year following transplantation. Equal numbers of patients received 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 disorder did not develop in any patient receiving dual therapy, and no further cases have been observed to a minimum of 2 years' follow-up. No other viral, fungal, or bacterial infectious complications were prevalent in patients treated with chRFT5.
Amlot
P L
PL
Department of Immunology, Royal Free Hospital School of Medicine, London, UK.
Rawlings
E
E
Fernando
O N
ON
Griffin
P J
PJ
Heinrich
G
G
Schreier
M H
MH
Castaigne
J P
JP
Moore
R
R
Sweny
P
P
D000328:Adult; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000917:Antibody Formation; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins