Combined IL-21 and Low-Dose IL-2 therapy induces anti-tumor immunity and long-term curative effects in a murine melanoma
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BioMed Central
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Combined IL-21 and Low-Dose IL-2 therapy induces anti-tumor immunity and long-term curative effects in a murine melanoma tumor model Hong He1, Preya Wisner1, Guojun Yang1, Hong-Ming Hu1, Dan Haley1, William Miller1, Aisling O'Hara1, W Gregory Alvord2, Christopher H Clegg3, Bernard A Fox1, Walter J Urba1 and Edwin B Walker*1 Address: 1Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland OR, USA, 2DMS-National Cancer Institute, Frederick MD, USA and 3Immunology Research, ZymoGenetics, Seattle WA, USA Email: Hong He - [email protected]; Preya Wisner - [email protected]; Guojun Yang - [email protected]; HongMing Hu - [email protected]; Dan Haley - [email protected]; William Miller - [email protected]; Aisling O'Hara - [email protected]; W Gregory Alvord - [email protected]; Christopher H Clegg - [email protected]; Bernard A Fox - [email protected]; Walter J Urba - [email protected]; Edwin B Walker* - [email protected] * Corresponding author
Published: 13 June 2006 Journal of Translational Medicine 2006, 4:24
doi:10.1186/1479-5876-4-24
Received: 10 April 2006 Accepted: 13 June 2006
This article is available from: http://www.translational-medicine.com/content/4/1/24 © 2006 He et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: In vivo studies have recently demonstrated that interleukin 21 (IL-21) enhances the anti-tumor function of T-cells and NK cells in murine tumor models, and the combined use of IL21 and IL-15 has resulted in prolonged tumor regression and survival in mice with previously established tumors. However, the combined anti-tumor effects of IL-21 and low dose IL-2 have not been studied even though IL-2 has been approved for human use, and, at low dose administration, stimulates the proliferation of memory T cells, and does not significantly increase antigen-induced apoptosis or regulatory T cell (Treg) expansion. This study examined whether recombinant IL-21 alone or in combination with low-dose IL-2 could improve the in vivo anti-tumor function of naïve, tumor-antigen specific CD8+ T cells in a gp10025–33 T cell receptor transgenic pmel murine melanoma model. Methods: Congenic C57BL/6 (Ly5.2) mice bearing subcutaneous B16F10 melanoma tumors were sublethally irradiated to induce lymphopenia. After irradiation naive pmel splenocytes were adoptively transferred, and mice were immunized with bone marrow-derived dendritic cells pulsed with human gp10025–33 (hgp10025–33). Seven days after vaccination groups of mice received 5 consecutive days of intraperitoneal administration of IL-2 alone (20 × 103 IU), IL-21 alone (20 µg) or IL-21 and IL-2. Control animals received no cytokine
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