Interleukin 21 enhances antibody-mediated tumor rejection

Cancer Research
Mark J SmythMichael H Kershaw

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.

Citations

Apr 30, 2010·Journal of Translational Medicine·Jennifer A WestwoodMichael H Kershaw
Sep 6, 2008·PloS One·Shrimati Datta, Nora E Sarvetnick
Jul 20, 2010·Immunotherapy·Takayuki YoshimotoJunichiro Mizuguchi
May 31, 2012·Immunotherapy·Holbrook E KohrtJoshua Brody
Oct 23, 2009·Tissue Antigens·H Søndergaard, K Skak
May 23, 2012·Experimental Hematology·Abdul Gafoor PuthiyaveetilDavid L Caudell
Jun 25, 2008·Current Opinion in Immunology·Nicole M HaynesMark J Smyth
May 15, 2013·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·John B Mumm, Martin Oft
Dec 30, 2009·International Journal of Cancer. Journal International Du Cancer·Michela CroceSilvano Ferrini
May 12, 2015·Journal of Immunology Research·Michela CroceSilvano Ferrini
Feb 27, 2010·BMC Cancer·Elizabeth A TindallVanessa M Hayes
May 6, 2006·Seminars in Immunology·Yoshihiro Hayakawa, Mark J Smyth
Sep 25, 2008·Nature Reviews. Cancer·Ricky W JohnstoneMark J Smyth

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