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Short-term therapy with anti-ICAM-1 monoclonal antibody induced long-term liver allograft survival in nonhuman primates

Authors
 Suk Kyun Hong  ;  Dongkyu Han  ;  Sun-Kyung Lee  ;  Jiyeon Kim  ;  Eung-Soo Hwang  ;  Haeryoung Kim  ;  Jae-Il Lee  ;  Kwangpyo Hong  ;  Eui Soo Han  ;  Jae-Hyung Cho  ;  Jeong-Moo Lee  ;  YoungRok Choi  ;  Kwang-Woong Lee  ;  Nam-Joon Yi  ;  Jaeseok Yang  ;  Kyung-Suk Suh 
Citation
 AMERICAN JOURNAL OF TRANSPLANTATION, Vol.21(9) : 2978-2991, 2021-09 
Journal Title
AMERICAN JOURNAL OF TRANSPLANTATION
ISSN
 1600-6135 
Issue Date
2021-09
Keywords
clinical research / practice, pancreas / simultaneous pancreas-kidney transplantation ; dclinical decision-making ; diabetes: type 2, diabetes : new onset / posttransplant ; endocrinology / diabetology ; health services and outcomes research ; immunosuppression / immune modulation ; obesity ; recipient selection
Abstract
Tolerance induction remains challenging following liver transplantation and the long-term use of immunosuppressants, especially calcineurin inhibitors, leads to serious complications. We aimed to test an alternative immunosuppressant, a chimeric anti-ICAM-1 monoclonal antibody, MD-3, for improving the outcomes of liver transplantation. We used a rhesus macaque liver transplantation model and monkeys were divided into three groups: no immunosuppression (n = 2), conventional immunosuppression (n = 4), and MD-3 (n = 5). Without immunosuppression, liver allografts failed within a week by acute rejection. Sixteen-week-long conventional immunosuppression that consisted of prednisolone, tacrolimus, and an mTOR inhibitor prolonged liver allograft survival; however, recipients died of acute T cell-mediated rejection (day 52), chronic rejection (days 62 and 66), or adverse effects of mTOR inhibitor (day 32). In contrast, 12-week-long MD-3 therapy with transient conventional immunosuppression in the MD-3 group significantly prolonged the survival of liver allograft recipients (5, 96, 216, 412, 730 days; p = .0483). MD-3 effectively suppressed intragraft inflammatory cell infiltration, anti-donor T cell responses, and donor-specific antibody with intact anti-cytomegalovirus antibody responses. However, this regimen ended in chronic rejection. In conclusion, short-term therapy with MD-3 markedly improved liver allograft survival to 2 years without maintenance of immunosuppressant. MD-3 is therefore a promising immune-modulating agent for liver transplantation.
Full Text
https://onlinelibrary.wiley.com/doi/10.1111/ajt.16486
DOI
10.1111/ajt.16486
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Yang, Jaeseok(양재석)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184880
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