Induction immunotherapy with IL-2Ra monoclonal antibody in kidney transplantation

Abstract

The development of new immunosuppressive agents is designed to reduce the incidence and severity of early acute post-transplant rejection. One potential target for more specific immunosuppressive therapy with monoclonal antibodies is the high affinity a chain of interleukin-2 receptors (IL-2Ra). Clinical investigation of murine IL-2Ra monoclonal antibodies (IL-2Ra mAb) in renal transplantation has indicated that a complete blockade of IL-2Ra during the critical first post-transplant months allows effective immunoprophylaxis, especially in the early post-transplant period. Efficacy of these agents, however, is hampered by their short disposition half-lives in humans and their immunogenicity in the form of neutralizing human antimouse antibodies. These inherent problems can be partially overcome by chi-meric, hyper-chimeric (humanized) products and multiple dose regimens. Both IL-2Ra mAbs: daclizumab (humanized) and basiliximab (chimeric) currently approved for clinical use have been found to reduce the frequency of acute rejections in renal transplant recipients without an apparent increase in short-term toxicities. In most transplant centers where these agents are utilized, they are being routinely administered as induction immunoprophylaxis in recommended multiple dose regimens to recipients of solid organ transplants. Others have restricted their use to certain high-risk patients such as those undergoing multi-organ transplantation, recipients with high panel-reactive antibodies, African-Americans, patients at risk for developing delayed graft function (DGF), and children. Recently some investigators have successfully administered these antibodies co-administered with newer immunosuppressive agents in limited dose protocols thus developing cost effective and simplified regimens. Therefore, in the absence of a favorable long-term efficacy, it is likely that these agents will be administered in limited dose protocols along with one of the modulators of IL-2, i.e. calcineurin inhibitors (CNI), to a selected group of patients in whom additional immunosuppression in the early post-transplantation period is desirable.