Treatment of acute kidney allograft rejection with a non-mitogenic CD3 antibody.
T3/4.A is a non-mitogenic murine IgA mAb to human CD3 that was selected for clinical studies to provide an alternative for the mitogenic, T cell-activating, therapeutic mAb OKT3. Previously, we reported that T3/4.A is better tolerated in humans than the IgG2a-CD3 mAb T3/4.2a. Here we report the results of a phase II clinical trial to assess the immunosuppressive potential of T3/4.A. Eighteen first kidney transplant recipients with a first rejection episode were included. Baseline immunosuppression consisted of cyclosporin and prednisolone. Rejection treatment consisted of 5 mg mAb per day during 10 days. Fourteen patients responded, of whom four experienced a second rejection within 2 weeks, one experienced chronic rejection after 2.5 years, whereas the others remained rejection-free after treatment (median duration of follow-up 42 months). Four patients did not respond and eventually lost their graft. These results are similar to treatment results with OKT3, as reported in the literature. Following the first dose of T3/4.A, side effects were limited, and reduced compared to OKT3-treated controls. On the second day, 15 patients developed transient vomiting and/or diarrhoea, which coincided with elevated serum levels of proinflammatory cytokines. Minimal or even no side effects occurred during the remaining days, which is in sharp contrast to that seen generally during OKT3 treatment. Both T cell numbers and TCR expression were reduced during the therapy. We conclude that T3/4.A is a good alternative for OKT3 to treat rejection episodes in renal transplant recipients.
Meijer
R T
RT
Academic Medical Center, University of Amsterdam, Division of Clinical Immunology and Rheumatology, Amsterdam, The Netherlands. r.j.tenberge@amc.uva.nl
Surachno
S
S
Yong
S L
SL
Bemelman
F J
FJ
Florquin
S
S
Ten Berge
I J M
IJ
Schellekens
P T A
PT
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D017252:CD3 Complex / Q000276:immunology*; D016572:Cyclosporine / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000401:mortality; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D015996:Survival Rate; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; D007070:Immunoglobulin A; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone