*Purpose: 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 outcomes of liver transplantation.

*Methods: We used a rhesus macaques liver transplantation model and monkeys were divided into three groups: no immunosuppression (n=2), conventional immunosuppression (n=4), and MD-3 (n=5).

*Results: 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 (day 62, 66) or adverse effects of mTOR inhibitor (day 32). In contrast, 12 weeks-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 = 0.0483). 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.

*Conclusions: 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.

« Back to 2021 American Transplant Congress