Monoclonal Antibodies in Solid Organ Transplantation

Abstract

In an attempt to target solid organ transplant immunosuppression, monoclonal antibodies directed against key steps in specific immunologic pathways were introduced. The first agent, muromonab-CD3 (OKT3), was initially introduced in the early 1980s for the treatment of allograft rejection. The use of monoclonal antibodies has evolved and expanded over the past two decades and today monoclonal antibodies are routinely included as part of the overall immunosuppression regimen. Both the innate and adaptive immune systems have multiple components and signal transduction pathways aimed at protecting the host from a foreign body, such as transplanted tissue. The ultimate goal of posttransplant immunosuppression is tolerance, a state in which the host immune system recognizes the foreign tissue but does not react to it. This goal has yet to be achieved under modern immunosuppression secondary to immune system redundancy as well as the toxicity of currently available agents. Therefore, monoclonal antibodies are used to provide targeted, immediate immunomodulation aimed at attenuating the overall immune response. Specifically, monoclonal antibodies have been used to (1) decrease the inherent immunoreactivity of the potential transplant recipient prior to engraftment, (2) induce global immunosuppression at the time of transplantation allowing for modified introduction of other immunosuppressive agents (calcineurin inhibitors or corticosteroids), (3) spare exposure to maintenance immunosuppressive agents, and (4) treat acute allograft rejection. Monoclonal antibody selection, as well as dose, is based on patient-specific factors, such as indication for transplantation, type of organ being transplanted, and the long-term immunosuppression objective.