title: Prolonged survival of allogeneic islets in cynomolgus monkeys after short-term triple therapy.
abstract: Preclinical studies in nonhuman primates (NHP) are particularly useful to evaluate the safety and efficacy of new therapeutic proteins developed for use in clinical transplantation. We hypothesized that a treatment that selectively destroys activated cytopathic donor reactive T cells while sparing resting and immunoregulatory T cells in a mouse model might also produce long-term drug-free engraftment and tolerance without the hazards of lymphopenia in the challenging nonhuman primate islet allograft model. Short-term treatment with a regimen consisting of rapamycin, and IL-2.Ig plus mutant antagonist-type IL-15.Ig cytolytic fusion proteins (triple therapy) posttransplantation results in prolonged, drug-free engraftment of cynomolgus islet allografts. Moreover slow progressive loss of islet function in some recipients was not associated with obvious pathologic evidence of rejection.
authors.affiliation: Harvard Medical School, Department of Surgery, Transplant Institute at Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Boston, MA, USA. mkoulman@bidmc.harvard.edu
authors.forename: M
authors.initials: M
authors.lastname: Koulmanda
authors.forename: A
authors.initials: A
authors.lastname: Qipo
authors.forename: Z
authors.initials: Z
authors.lastname: Fan
authors.forename: N
authors.initials: N
authors.lastname: Smith
authors.forename: H
authors.initials: H
authors.lastname: Auchincloss
authors.forename: X X
authors.initials: XX
authors.lastname: Zheng
authors.forename: T B
authors.initials: TB
authors.lastname: Strom
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D006085:Graft Survival; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D019409:Interleukin-15 / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects; D008252:Macaca fascicularis; D051379:Mice; D020123:Sirolimus / Q000627:therapeutic use*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D019409:Interleukin-15; D007376:Interleukin-2; D020123:Sirolimus