Prophylactic use of the IL-2 receptor-specific monoclonal antibody LO-Tact-1 with cyclosporin A and steroids in renal transplantation

  • C. Hiesse
  • F. Kriaa
  • B. Charpentier
  • D. Fries
  • P. Alard
  • O. Lantz
  • J. Noury
  • H. Bensadoun
  • G. Benoit
  • H. Bazin
Conference paper

Abstract

LO-Tact-1 is a rat anti-human monoclonal antibody which is directed to the 55-kDa α-chain of the interleukin 2 (IL2) receptor. We conducted a pilot trial in 15 first-time cadaveric renal transplant patients undergoing for immunosuppression a 14-day course of LO-Tact-1 (10 mg IV daily) together with cyclosporine, low dose steroids (0.5 mg/kg) and azathioprine. Results showed a good immunosuppressive effect, as measured by the similar incidence of acute rejection episodes (0.6 per patient) when compared with 20 patients treated during the same period with our standard quadruple prophylactic combination with higher initial doses of steroids (2 mg/kg) and antilymphocyte globulin (ALG) instead of LO-Tact-1 (0.4 per patient). At 2 years post-transplant, graft survival was 93%, and only 1 patient lost his kidney by rejection. No local or general adverse effect of antibody administration was encountered, and haematological changes remained of minor importance. Local bacterial infection was observed in 3 patients, but viral diseases (including cytomegalovirus, CMV) remained exceptional. In contrast, severe clinical CMV infections occurred in 3 patients (15%) treated by ALG. Nine of 15 patients developed rat-specific antibodies, but only 4 before the completion of LO-Tact-1 treatment, without any correlation with the further development of acute rejection. Patients who suffered rejection had lower LO-Tact-1 levels and higher soluble IL2 receptor levels during the period of infusion, suggesting the crucial importance of pharmacokinetic monitoring to adjust individual doses.

Key words

Interleukin 2 receptor Monoclonal antibodies Renal graft rejection 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • C. Hiesse
    • 1
  • F. Kriaa
    • 1
  • B. Charpentier
    • 1
  • D. Fries
    • 1
  • P. Alard
    • 2
  • O. Lantz
    • 2
  • J. Noury
    • 3
  • H. Bensadoun
    • 4
  • G. Benoit
    • 4
  • H. Bazin
    • 5
  1. 1.Departments of NephrologyHôpital de Bicêtre, Université Paris-SudParisFrance
  2. 2.Laboratory of Cellular Immunology and TransplantationER277 CNRS, Institut de Recherches Scientifiques sur le CancerVillejuifFrance
  3. 3.InnopharmBoulogne-BillancourtFrance
  4. 4.Departments of UrologyHôpital de Bicêtre, Université Paris-SudParisFrance
  5. 5.Experimental Immunology UnitUniversité Catholique de LouvainBrusselsBelgium

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