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Soluble Interleukin-13R2 Decoy Receptor Inhibits Hodgkin’s Lymphoma Growth in Vitro and in Vivo

¹ Division of Experimental Therapeutics, Toronto General Research Institute, McLaughlin Centre for Molecular Medicine, and ² Advanced Medical Discovery Institute, Departments of Immunology and Medical Biophysics, University Health Network, University of Toronto, Toronto, Ontario, Canada

Recent studies have demonstrated that the malignant Reed-Sternberg cells of Hodgkin’s lymphoma (HL) secrete and are responsive to interleukin (IL)-13. We hypothesized that overexpression of a soluble IL-13 decoy receptor (sIL-13R2) via adenoviral-mediated gene transfer would inhibit IL-13-induced Reed-Sternberg cell proliferation. Western blot and ELISA analysis verified expression of sIL-13R2 in cell lysates and supernatants of AdsIL-13R2-transduced COS-7 cells. Treatment of two IL-13-responsive HL-derived cell lines, HDLM-2 and L-1236, with AdsIL-13R2-conditioned medium, resulted in the inhibition of cell proliferation, and down-regulated the phosphorylation of signal transducer and activator of transcription 6 (STAT6), an important mediator of IL-13 signaling. i.v. delivery of AdsIL-13R2 in NOD/SCID mice with s.c. implanted HDLM-2 cells delayed tumor onset and growth while enhancing survival compared with control mice. Intratumoral administration of AdsIL-13R2 led to the regression or stabilization of established tumors and was associated with diminished STAT6 phosphorylation. Our data demonstrate that AdsIL-13R2 can suppress HL growth in vitro and in vivo.

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