title: Prolongation of primate renal allograft survival by anti-Tac, an anti-human IL-2 receptor monoclonal antibody.
abstract: 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.
authors.affiliation: Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: M H
authors.initials: MH
authors.lastname: Reed
authors.forename: M E
authors.initials: ME
authors.lastname: Shapiro
authors.forename: T B
authors.initials: TB
authors.lastname: Strom
authors.forename: E L
authors.initials: EL
authors.lastname: Milford
authors.forename: C B
authors.initials: CB
authors.lastname: Carpenter
authors.forename: D S
authors.initials: DS
authors.lastname: Weinberg
authors.forename: K A
authors.initials: KA
authors.lastname: Reimann
authors.forename: N L
authors.initials: NL
authors.lastname: Letvin
authors.forename: T A
authors.initials: TA
authors.lastname: Waldmann
authors.forename: R L
authors.initials: RL
authors.lastname: Kirkman
mesh_terms: 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
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D015375:Receptors, Interleukin-2