INTRODUCTION
Administration of targeted immunosuppression, in the form of genetically
engineered antibodies, is commonplace in solid organ transplantation.
Polyclonal antibodies, such as rabbit anti-thymocyte globulin, offer global
immunosuppression by target-ing several cell surface antigens on B- and
T-lymphocytes. However, secondary to their broad therapeutic targets, they are
associated with infection, infusion related reactions, inter-batch variability,
and post-transplant malignancy. Nevertheless, polyclonal antibodies are still
commonly administered for in-duction and treatment of allograft rejection and
offer an important role in current solid organ transplanta-tion, which is
beyond the scope of this chapter.
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, was initially introduced in the early 1980s for the
treatment of allograft rejection (Morris, 2004). The use of monoclonal
antibodies has evolved and expanded over the past two decades and today are
routinely included as part of the overall immunosuppression regimen. Both the
innate and adaptive immune systems have multiple components and signal
trans-duction pathways aimed at protecting the host from a foreign body, such
as transplanted tissue. The ultimate goal of post-transplant 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 immunomo-dulation aimed at attenuating the overall
immune response. Specifically, monoclonal antibodies have been used to (1)
decrease the inherent immunoreac-tivity 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. To understand the
approach that the transplant clinician uses to deter-mine which agent to
administer and when, it is necessary to briefly describe how immunoreactivity
can be predicted and review the immunological basis for the use and development
of monoclonal anti-bodies in solid organ transplantation.
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