Role of anti-interleukin-2 receptor antibodies in kidney transplantation

Abstract

From the early 1960s, the mainstay of immunosuppression for kidney transplantation has been corticosteroids. Since then, many new drugs have been developed to maintain the renal allograft. Current maintenance immunosuppression commonly consists of corticosteroids, antiproliferative agents and calcineurin inhibitors (e.g. cyclosporin). More recently, antihuman antibodies, either monoclonal or polyclonal, have been developed to use for induction at the time of transplantation or to treat rejection. With the advances in molecular technology, a new class of antihuman antibodies [the anti-interleukin-2 receptor (IL-2R) antibodies] has emerged that incorporate a murine antigen-binding site on to a human immunoglobulin backbone. Such methodology creates antihuman antibodies with high affinity for the epitope and with prolonged serum antibody half-lives. Interleukin-2 and its receptor are central to lymphocyte activation and are the main targets of calcineurin inhibitors. In addition, the anti-IL-2R antibodies inhibit a key target in immune activation. Daclizumab and basiliximab have been shown to significantly reduce the incidence of acute rejection in kidney transplantation. Since these anti-IL-2R antibodies are well tolerated and since calcineurin inhibitors are intrinsically nephrotoxic, anti-IL-2R antibodies have been used in an attempt to avoid cyclosporin after transplantation. Data from clinical trials seem to indicate that the addition of an anti-IL-2R antibody is not sufficient to warrant complete withdrawal of calcineurin inhibitors for more than a very short period after transplantation. A more promising role for anti-IL-2R antibodies may be in renal transplant recipients with delayed graft function (DGF). Recent data on the use of either low-dose calcineurin inhibitors or sirolimus (rapamycin) in conjunction with the anti-IL-2R antibodies for patients with DGF showed no increased risk of acute rejection. Long-term graft survival with use of these low-dose calcineurin inhibitor protocols has yet to be established.