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Adenoviral Gene Transfer of Stromal Cell–Derived Factor-1 to Murine Tumors Induces the Accumulation of Dendritic Cells and Suppresses Tumor Growth

¹ Division of Pulmonary and Critical Care Medicine and ² Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

Requests for reprints: Ronald G. Crystal, Department of Genetic Medicine, Weill Medical College of Cornell University, 515 East 71st Street, Suite S-1000, New York, NY 10021. Phone: 212-746-2258; Fax: 212-746-8383; E-mail: geneticmedicine{at}med.cornell.edu.

The human CXC chemokine, stromal cell–derived factor 1 (SDF-1), is known to function in vitro as a chemotactic factor for lymphocytes, monocytes, and dendritic cells. In the context that dendritic cells are powerful antigen-presenting cells, we hypothesized that adenoviral gene transfer of SDF-1 to tumors might inhibit growth of preexisting tumors through attracting dendritic cells to the tumor. AdSDF-1 mediated the expression of SDF-1 mRNA and protein in A549 cells in vitro, and the supernatant of the AdSDF-1-infected A549 cells showed chemotactic activity for dendritic cells. When syngeneic murine CT26 colon carcinoma tumors (BALB/c) and B16 melanoma and Lewis lung cell carcinoma (C57Bl/6) were injected with AdSDF-1 (5 x 10⁸ plaque-forming units), there was an accumulation of dendritic cells and CD8⁺ cells within the tumor and significant inhibition of tumor growth compared with tumors injected with PBS or AdNull (control vector). The injection of AdSDF-1 into tumors induced the inflammatory enlargement and the accumulation of dendritic cells in the draining lymph node. Intratumoral AdSDF-1 administration elicited tumor-specific CTLs and adoptive transfer of splenocytes from AdSDF-1-treated mice resulted in the elongation of survival after tumor challenge. Interestingly, in wild-type and CD4^–/– mice but not in CD8^–/– mice, AdSDF-1 inhibited the growth of the tumor. These observations suggest that adenoviral gene transfer of SDF-1 may be a useful strategy to accumulate dendritic cells in tumors and evoke antitumor immune responses to inhibit tumor growth. (Cancer Res 2006; 66(7): 3513-22)

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