title: Interleukin 21 enhances antibody-mediated tumor rejection.
abstract: Interleukin-21 (IL-21) is a cytokine with structural and sequence homology to IL-2 and IL-15 that has antitumor activity alone in mouse experimental tumor models and a tolerable safety profile in phase I trials in patients with metastatic melanoma and renal cell carcinoma. Several monoclonal antibodies (mAb) targeted at tumor-associated antigens also have improved antitumor activities in mice when used in combination with IL-21. Recently, we described a rational three antibody-based approach (triple mAb, TrimAb) to eradicating established mouse tumors that required the generation of tumor-reactive CD8(+) T cells and IFN-gamma. Herein, we show that sequentially combining TrimAb with recombinant IL-21 can significantly improve the antitumor activity of this combination against very advanced disease. These data further support the use of IL-21 in adjuvant settings where strong T cell-mediated immune responses to tumors can be generated.
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Center, East Melbourne, Victoria, Australia. mark.smyth@petermac.org
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: Michele W L
authors.initials: MW
authors.lastname: Teng
authors.forename: Janelle
authors.initials: J
authors.lastname: Sharkey
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Westwood
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Haynes
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Pallavur V
authors.initials: PV
authors.lastname: Sivakumar
authors.forename: Michael H
authors.initials: MH
authors.lastname: Kershaw
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000276:immunology; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006801:Humans; D007371:Interferon-gamma / Q000172:deficiency; D007378:Interleukins / Q000276:immunology* / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000276:immunology; D008212:Lymphocyte Depletion; D008545:Melanoma / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology*; D054353:Perforin / Q000172:deficiency; D013601:T-Lymphocytes / Q000276:immunology; D000098546:Interleukin-21
chemical_list: D000912:Antibodies, Neoplasm; D007378:Interleukins; D054353:Perforin; D007371:Interferon-gamma; D000098546:Interleukin-21