ANTIBODY-TARGETED CYCLOSPORINE-A

The aim of this study was to test the pharmacological effectiveness of antibody-targeted cyclosporin A. Only free drug is currently availabl e; its administration is accompanied by nephrotoxicity, hepatotoxicity and neurotoxicity which severely limits the treatment. Moreover, due to the high nonspecific binding to a number of tissues, the therapeuti c doses are considerably higher than required for the actual treatment . We suggest using antibody-targeted CsA conjugate based on a water-so luble synthetic copolymer of N-(2-hydroxypropyl)methacrylamide to over come these problems. In this construct the antibody to T lymphocyte su bsets (anti-CD3 in human and anti-Thy 1.2 in mouse) is responsible for the specific delivery which limits the drug action to the target tiss ue. Antibody-targeted CsA effectively inhibits lectin- and alloantigen -induced T cell proliferation and considerably reduces CsA nephrotoxic ity.