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Effect of the Tumor Specific Antibody-IL 2 Fusion Protein on Established Pulmonary and Hepatic Metastases

Induction of a T-cell mediated antitumor response is the ultimate goal for tumor immunotherapy. We demonstrate here that antibody-targeted IL2 therapy is effective against established pulmonary and hepatic melanoma metastases in a syngeneic murine tumor model. The effector mechanisms involved in this tumor eradication are not dependent on N K cells, since the therapeutic effect of antibody-IL2 fusion protein was not altered in NK cell-deficient mice. In contrast, T cells are essential for the observed antitumor effect, since therapy with antibody-IL2 fusion proteins is unable to induce tumor eradication in T cell-deficient SCID mice. In vivo depletion studies characterized the essential effector cell population further as CD8+ T cells. Such C D 8 + T cells, isolated from tumor bearing mice after antibody-directed IL2 therapy, exerted a M H C class I-restricted cytotoxicity against the same tumor in vitro. These data demonstrate the ability of antibody-targeted IL2 delivery to induce a T cell--dependent host immune response that is capable of eradicating established melanoma metastases in clinically relevant organs.