Daclizumab: novel biologic immunoprophylaxis for prevention of acute rejection in renal transplantation

Abstract

THE 1990s have witnessed the introduction of several exciting new small molecules used for maintenance immunosuppression such as mycophenolate mofetil (MMF), tacrolimus, and sirolimus. However, as we approach the millennium, new humanized biologic agents are being introduced or are in clinical development. They promise to optimize immunosuppression by providing selectivity, excellent tolerability, and the potential for inducing tolerance. In the past year, two monoclonal antibodies (MAbs), a chimeric and a humanized targeting the anti– interleukin-2 receptor (IL-2R), have been shown to be effective in reducing acute rejection in renal transplant recipients without producing overimmunosuppression and additional side effects. The major advantage of targeting the a chain of the IL-2R is that it is expressed predominantly on activated T cells and its expression is essential for the formation of the high-affinity IL-2R. Interaction of IL-2 with the high-affinity IL-2R is required for clonal expansion and continued viability of activated T cells. Blockade of this pathway can result in effective and selective immunosuppression. Daclizumab is a humanized MAb with an IgG1 backbone that retains almost exclusively the complementary determining regions from its murine antiTac parent antibody, binds with high affinity to the a chain of the IL-2R, and blocks IL-2R–mediated biologic responses. The half-life of daclizumab is 20 days, which is comparable to human IgG.