JAK3 inhibitor-based immunosuppression in allogeneic islet transplantation in cynomolgus monkeys

Jong Min Kim, Jun Seop Shin, Byoung Hoon Min, Seong Jun Kang, Il Hee Yoon, Hyunwoo Chung, Jiyeon Kim, Eung Soo Hwang, Jongwon Ha, Chung Gyu Park

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Islet transplantation is efficacious to prevent severe hypoglycemia and glycemic liability of selected patients of type 1 diabetes. However, since calcineurin inhibitor (CNI) causes β-cell and nephrotoxicity, alternative drug(s) with similar potency and safety profile to CNI will be highly desirable. Here we tested whether JAK3 inhibitor, tofacitinib could be used instead of tacrolimus in CIT07 immunosuppression regimen in cynomolgus nonhuman primate (NHP) model. Five independent streptozotocin (STZ)-induced diabetic monkeys were transplanted with MHC-mismatched allogeneic islets and three animals were further re-transplanted upon insufficient glycemic control or early islet graft rejection. After islet transplantation, blood glucose levels were quickly stabilized and maximal islet graft survival as measured by serum C-peptide concentration was >330, 98, >134, 31, or 22 days, respectively, after transplantation (median survival day; 98 days). Cellular and humoral immune responses were efficiently suppressed by JAK3 inhibitor-based immunosuppression during the follow-up periods. Although intermittent increases of the genome copy number of cynomolgus cytomegalovirus (CMV) were detected by quantitative real-time PCR analyses, serious infections or posttransplant lymphoproliferative disease (PTLD) was not found in all animals. Taken together, we have shown that JAK3 inhibitor could be used in replacement of tacrolimus in a highly translatable NHP islet transplantation model and these results suggest that JAK3 inhibitor will be potentially incorporated in human allogeneic islet transplantation.

Original languageEnglish
Pages (from-to)119-128
Number of pages10
JournalIslets
Volume11
Issue number5
DOIs
StatePublished - Sep 3 2019

Keywords

  • Calcineurin inhibitor
  • Islet transplantation
  • JAK3 inhibitor
  • NHP

Fingerprint

Dive into the research topics of 'JAK3 inhibitor-based immunosuppression in allogeneic islet transplantation in cynomolgus monkeys'. Together they form a unique fingerprint.

Cite this