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

The human CXC chemokine, stromal cell–derived factor 1 (SDF-1A), 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-1A to tumors might inhibit growth of preexisting tumors through attracting dendritic cells to the tumor. AdSDF-1Amediated the expression of SDF-1A mRNA and protein in A549 cells in vitro, and the supernatant of the AdSDF-1A-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-1A (5 10 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-1A into tumors induced the inflammatory enlargement and the accumulation of dendritic cells in the draining lymph node. Intratumoral AdSDF-1A administration elicited tumor-specific CTLs and adoptive transfer of splenocytes from AdSDF-1A-treated mice resulted in the elongation of survival after tumor challenge. Interestingly, in wild-type and CD4 / mice but not in CD8 / mice, AdSDF-1A inhibited the growth of the tumor. These observations suggest that adenoviral gene transfer of SDF-1Amay 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)