Prophylactic use of the IL-2 receptor-specific monoclonal antibody LO-Tact-1 with cyclosporin A and steroids in renal transplantation.
LO-Tact-1 is a rat anti-human monoclonal antibody which is directed to the 55-kDa alpha-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 i.v. 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.
Hiesse
C
C
Department of Nephrology, Hôpital de Bicêtre, Université Paris-Sud, Paris, France.
Kriaa
F
F
Alard
P
P
Lantz
O
O
Noury
J
J
Bensadoun
H
H
Benoit
G
G
Charpentier
B
B
Fries
D
D
Bazin
H
H
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000187:drug effects; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000453:epidemiology*; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007239:Infections / Q000453:epidemiology; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality; D011183:Postoperative Complications / Q000145:classification / Q000453:epidemiology; D011336:Probability; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D015996:Survival Rate; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D016572:Cyclosporine