Prolongation of primate renal allograft survival by anti-Tac, an anti-human IL-2 receptor monoclonal antibody.
In an effort to produce specific immunosuppression through the targeting of those lymphocytes expressing cell surface interleukin 2 receptors in response to an allograft, the anti-human IL-2 receptor monoclonal antibody anti-Tac was administered to cynomolgus monkeys receiving renal transplants. The data demonstrate that anti-Tac produces a significant delay in renal allograft rejection and prolongs host survival in cynomolgus monkeys. Though higher doses of anti-Tac produce modest delays in rejection, there was a surprising finding of greatly prolonged survival in three of five monkeys treated with much lower doses of anti-Tac. Anti-Tac was not shown to be synergistic with cyclosporine in this model. Animals treated with anti-Tac developed high titers of antibodies against the murine monoclonal antibody after 6-8 days of treatment, associated with the disappearance of plasma anti-Tac staining of activated lymphocytes as measured by flow cytometry. The data confirm the utility of the IL-2 receptor as a target for immunosuppressive therapy, and suggest that investigations of dosage and of methods to reduce the immunogenicity of anti-IL-2 receptor agents may be beneficial.
Reed
M H
MH
Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Shapiro
M E
ME
Strom
T B
TB
Milford
E L
EL
Carpenter
C B
CB
Weinberg
D S
DS
Reimann
K A
KA
Letvin
N L
NL
Waldmann
T A
TA
Kirkman
R L
RL
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics; D003524:Cyclosporins / Q000008:administration & dosage; D004306:Dose-Response Relationship, Immunologic; D006085:Graft Survival; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D008252:Macaca fascicularis; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013997:Time Factors
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D015375:Receptors, Interleukin-2