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 NK 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 CD8 + T cells, isolated from tumor bearing mice after antibody-directed IL2 therapy, exerted a MHC 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.
T cell-mediated eradication of murine metastatic melanoma induced by targeted interleukin 2 therapy.
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J C Becker, J D Pancook, S D Gillies, K Furukawa, R A Reisfeld; T cell-mediated eradication of murine metastatic melanoma induced by targeted interleukin 2 therapy.. J Exp Med 1 May 1996; 183 (5): 2361–2366. doi: https://doi.org/10.1084/jem.183.5.2361
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