HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fan, K. Articles by Yi, T. Search for Related Content PubMed PubMed Citation Articles by Fan, K. Articles by Yi, T.

Sodium Stibogluconate Interacts with IL-2 in Anti-Renca Tumor Action via a T Cell-Dependent Mechanism in Connection with Induction of Tumor-Infiltrating Macrophages¹

Keke Fan^*, Ming Zhou, Manas K. Pathak^*, Daniel J. Lindner, Cengiz Z. Altuntas, Vincent K. Tuohy, Ernest C. Borden^*, and Taolin Yi^2,*,

^* Department of Cancer Biology, Department of Immunology, Lerner Research Institute, Department of Anatomic Pathology, and Taussig Cancer Center, The Cleveland Clinic Foundation, Cleveland, OH 44195

IL-2 therapy results in 10–20% response rates in advanced renal cell carcinoma (RCC) via activating immune cells, in which the protein tyrosine phosphatase Src homology 2 domain-containing phosphatase 1 (SHP-1) is a key negative regulator. Based on finding that sodium stibogluconate (SSG) inhibited SHP-1, the anti-RCC potential and action mechanism of SSG and SSG/IL-2 in combination were investigated in a murine renal cancer model (Renca). Despite its failure to inhibit Renca cell proliferation in cultures, SSG induced 61% growth inhibition of Renca tumors in BALB/c mice coincident with an increase (2-fold) in tumor-infiltrating macrophages (M). A combination of SSG and IL-2 was more effective in inhibiting tumor growth (91%) and inducing tumor-infiltrating M (4-fold), whereas IL-2 alone had little effect. M increases were also detected in the spleens of mice treated with SSG (3-fold) or SSG/IL-2 in combination (6-fold), suggesting a systemic M expansion similar to those in SHP-deficient mice. T cell involvement in the anti-Renca tumor action of the combination was suggested by the observations that the treatment induced spleen IFN- T cells in BALB/c mice, but failed to inhibit Renca tumor growth in athymic nude mice and that SSG treatment of T cells in vitro increased production of IFN- capable of activating tumoricidal M. The SSG and SSG/IL-2 combination treatments were tolerated in the mice. These results together demonstrate an anti-Renca tumor activity of SSG that was enhanced in combination with IL-2 and functions via a T cell-dependent mechanism with increased IFN- production and expansion/activation of M. Our findings suggest that SSG might improve anti-RCC efficacy of IL-2 therapy by enhancing antitumor immunity.

This article has been cited by other articles:

				Q. Zhu, Y. Oei, D. B. Mendel, E. N. Garrett, M. B. Patawaran, P. W. Hollenbach, S. L. Aukerman, and A. J. Weiner Novel robust hepatitis C virus mouse efficacy model. Antimicrob. Agents Chemother., October 1, 2006; 50(10): 3260 - 3268. [Abstract] [Full Text] [PDF]