Adenoviral gene transfer of stromal cell-derived factor-1 to Murine tumors induces the accumulation of dendritic cells and suppresses tumor growth

The human CXC chemokine, stromal cell-derived factor 1 (SDF-1 alpha), is known to function in vitro its 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 alpha. to tumors might inhibit growth of preexisting tumors through attracting dendritic cells to file tumor. AdSDF-1 alpha mediated the expression of SDF-1 alpha-mRNA and protein in A549 cells in vitro, and the supernatant of the AdSDF-1 alpha-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 (C57B1/6) were injected with AdSDF-1 alpha (5 X 10(8) plaque-forming units), there was all 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 alpha into tumors induced the inflammatory enlargement and the accumulation of dendritic cells in the draining lymph node. Intratumoral AdSDF-1 alpha administration elicited turnor-specific CTLs and adoptive transfer of splenocytes from AdSDF-1 alpha-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 alpha inhibited the growth of the tumor. These observations suggest that adenoviral gene transfer of SDF-1 alpha may be a useful strategy to accumulate dendritic cells in tumors and evoke antitumor immune responses to inhibit tumor growth.