T-CELL-MEDIATED ERADICATION OF MURINE METASTATIC MELANOMA INDUCED BY TARGETED INTERLEUKIN-2 THERAPY

Induction of a T-cell mediated antitumor response is the ultimate goal for tumor immunotherapy. We demonstrate here that antibody-targeted I L2 therapy is effective against established pulmonary and hepatic mela noma metastases in a syngeneic murine tumor model. The effector mechan isms involved in this tumor eradication are not dependent on NK cells, since the therapeutic effect of antibody-IL2 fusion protein was not a ltered in NK cell-deficient mice. In contrast, T cells are essential f or the observed antitumor effect, since therapy with antibody-IL2 fusi on proteins is unable to induce tumor eradication in T cell-deficient SCID mice. In vivo depletion studies characterized the essential effec tor cell population further as CD8+ T cells. Such CD8+ T cells, isolat ed from tumor bearing mice after antibody-directed IL2 therapy, exerte d a MHC class I-restricted cytotoxicity against the same tumor in vitr o. These data demonstrate the ability of antibody-targeted IL2 deliver y to induce a T cell-dependent host immune response that is capable of eradicating established melanoma metastases in clinically relevant or gans.