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

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, Young Rok Choi, Kwang Woong Lee, Nam Joon Yi, Jaeseok Yang, Kyung Suk Suh

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2978-2991
Number of pages14
JournalAmerican Journal of Transplantation
Volume21
Issue number9
DOIs
StatePublished - Sep 2021
Externally publishedYes

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

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