Prophylactic use of monoclonal anti-IL-2 receptor antibody in cadaveric renal transplantation.
In vivo administration of an anti-interleukin-2 (anti-IL-2) receptor monoclonal antibody is a potential new therapy for prevention of allograft rejection of a freshly transplanted organ. Such an approach is more selective than targeting all T cells, or even the CD4 or CD8 major subsets, because only the very recently activated cells should be affected. A clinical trial of anti-Tac monoclonal antibody is in progress in which 20 mg of the immunoglobulin G 2a (lgG2a) antibody is administered intravenously daily for 10 days after cadaveric renal transplantation. Combinations with and without azathioprine, and with varying doses of cyclosporine with prednisone, are being evaluated in a randomized trial. Results to date show a significant immunosuppressive effect of anti-Tac, as measured by a reduced incidence and later onset of acute rejection episodes compared with cyclosporine plus prednisone or cyclosporine plus azathioprine plus prednisone. Removal or cytodestruction of IL-2-receptor positive cells from the peripheral blood does not occur to any major degree, even though serum levels of the antibody are always detectable. In addition, functional studies of MLR, CML, and suppressor cell generation 4 days after cessation of anti-Tac administration show no significant difference between treated and control groups The effect of anti-Tac seems, therefore, to be limited to inhibition of IL-2-mediated T-cell growth during the period of administration, with recovery after a few days' lag period.
Carpenter
C B
CB
Department of Medicine Brigham and Women's Hospital, Boston, MA 02115.
Kirkman
R L
RL
Shapiro
M E
ME
Milford
E L
EL
Tiney
N L
NL
Waldmann
T A
TA
Zimmerman
C E
CE
Ramos
E L
EL
Strom
T B
TB
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002102:Cadaver; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D016032:Randomized Controlled Trials as Topic; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2