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 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.
Becker
J C
JC
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
Pancook
J D
JD
Gillies
S D
SD
Furukawa
K
K
Reisfeld
R A
RA
D000818:Animals; D000911:Antibodies, Monoclonal; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary* / Q000628:therapy; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary* / Q000628:therapy; D008212:Lymphocyte Depletion; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2