Korean J Transplant.  2023 Nov;37(Suppl 1):S143. 10.4285/ATW2023.F-7280.

MD-3 maintenance therapy for liver allotransplantation in nonhuman primate

• Han D
• Hong S
• Choi Y
• Lee KW
• Suh KS
• Yi NJ
• Yang J

• KMID: 2551763
• DOI: http://doi.org/10.4285/ATW2023.F-7280

Abstract

MD-3 is a monoclonal antibody targeting intercellular adhesion molecule-1 (ICAM-1) in humans. Its unique property lies in its ability to promote tolerogenic myeloid cells and induce donor-specific T cell unresponsiveness instead of inhibiting cell adhesion. In previous nonhuman primate (NHP) studies, a short-term (3 months) administration of MD-3 effectively suppressed liver allograft rejection and extended allograft survival. However, over time, chronic rejection and graft failure became evident. Building on these promising findings, our current investigation sought to explore whether MD-3 could serve as an alternative to toxic calcineurin inhibitors for long-term maintenance therapy. Using a Rhesus macaque liver transplantation model, we divided the animals into three groups: a no immunosuppression group (n=2), a conventional immunosuppression group (n=4) receiving standard treatment, and an MD-3 maintenance group (n=4). The no immunosuppression group experienced severe acute allograft rejection and had very short allograft survival. The conventional immunosuppression group exhibited acute or chronic allograft rejection and eventually lost their liver allografts. In contrast, the MD-3 maintenance group showed prolonged liver allograft survival with only one member experiencing allograft loss due to liver cirrhosis related to hepatic venous obstruction. The remaining three members in the MD-3 maintenance group maintained well-functioning liver allografts (POD853, 888, 1364). During the protocol biopsies, one member in the MD-3 group displayed mild liver function abnormalities and mild acute T cell-mediated rejection, while the other two showed normal liver function and no signs of rejection. Notably, the MD-3 trough levels were lower in the member who experienced mild rejection compared to the other members of the MD-3 maintenance group. Overall, our study demonstrates that long-term MD-3 mono-maintenance therapy effectively suppresses liver allograft rejection and sustains allograft survival without the need for conventional immunosuppressants, including calcineurin inhibitors.