Adenovirus-mediated gene delivery of the soluble IL-13 decoy receptor inhibits Hodgkin lymphoma growth in vitro and in vivo.

摘要

The malignant Reed-Sternberg (RS) cells of Hodgkin lymphoma (HL) secrete and are responsive to interleukin (IL)-13. We hypothesized that over-expression of a soluble IL-13 decoy receptor (sIL-13Ralpha2) via adenoviral-mediated gene transfer would inhibit IL-13 induced RS cell proliferation. Treatment of two HL-derived cell lines, HDLM-2 and L-1236, with AdsIL-13Ralpha2 conditioned media resulted in the inhibition of cell proliferation, and down-regulated the phosphorylation of signal transducer and activator of transcription 6 (STAT6). Gene expression profiling on HDLM-2 cells treated with sIL-13Ralpha2 revealed 63 differentially expressed genes including MFG-E8, ITK, IkappaBalpha, IL-9, TRAIL, and CISH. Intravenous delivery of AdsIL-13Ralpha2 in tumour challenged NOD/SLID mice delayed tumour onset and growth, while enhancing survival compared to control mice. Intratumoural administration of AdsIL-13Ralpha2 led to the regression or stabilization of established tumours and was associated with decreased STAT6 phosphorylation. These results demonstrate that AdsIL-13Ralpha2 can suppress Hodgkin lymphoma growth in vitro and in vivo.