[Interleukin 21 enhances antibody-mediated tumor rejection]
>> Cancer Res. 2008 Apr 15;68(8):3019-25.
Interleukin 21 enhances antibody-mediated tumor rejection.
Smyth MJ, Teng MW, Sharkey J, Westwood JA, Haynes NM, Yagita H, Takeda K, Sivakumar PV, Kershaw MH.
Cancer Immunology Program, Peter MacCallum Cancer Center, East Melbourne, Victoria, Australia. mark.smyth@petermac.org
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.<<
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