Short‐term therapy with anti‐ICAM‐1 monoclonal antibody induced long‐term liver allograft survival in nonhuman primates. Issue 9 (8th February 2021)

• Record Type: Journal Article
• Authors: Hong, Suk Kyun; Han, Dongkyu; Lee, Sun‐Kyung; Kim, Jiyeon; Hwang, Eung‐Soo; Kim, Haeryoung; Lee, Jae‐Il; Hong, Kwangpyo; Han, Eui Soo; Cho, Jae‐Hyung; Lee, Jeong‐Moo; Choi, YoungRok; Lee, Kwang‐Woong; Yi, Nam‐Joon; Yang, Jaeseok; Suh, Kyung‐Suk
• Is Part Of: American journal of transplantation. Volume 21:Issue 9(2021)
• Page Start: 2978
• Page End: 2991
• Publication Date: 2021-02-08
• Subjects: health services and outcomes research -- clinical research / practice, pancreas / simultaneous pancreas‐kidney transplantation -- immunosuppression / immune modulation -- endocrinology / diabetology -- recipient selection -- diabetes: type 2, diabetes: new onset / posttransplant -- dclinical decision‐making -- obesity; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.16486
• Languages: English
• ISSNs: 1600-6135

Abstract

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. Abstract : In rhesus macaques, short‐term therapy with a chimeric anti‐ICAM‐1 antibody suppresses alloimmune T cell responses and donor‐ specific antibody, thereby markedly improving liver allograft survival up to 2 years without maintenance immunosuppression.