Premium
Prolonged Survival of Allogeneic Islets in Cynomolgus Monkeys After Short‐Term Triple Therapy
Author(s) -
Koulmanda M.,
Qipo A.,
Fan Z.,
Smith N.,
Auchincloss H.,
Zheng X. X.,
Strom T. B.
Publication year - 2012
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2012.03973.x
Subject(s) - medicine , islet , immunology , transplantation , cancer research , diabetes mellitus , endocrinology
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.