Immunization with TGF-β antisense oligonucleotide-modified autologous tumor vaccine enhances the antitumor immunity of MBT-2 tumor-bearing mice through upregulation of MHC class I and Fas expressions

The major purpose of this study was to define if the immunosuppressive effect of a transforming growth factor-β (TGF-β)-producing autologous tumor vaccine can be abrogated and rendered immunogenic by suppressing its TGF-β secretion with antisense strategy. In this study, using a TGF-β antisense gene modified MBT-2 tumor cell line [MBT-2/TGF-β(-) 3] which we established by ourselves, we first demonstrated that the amounts of TGF-β produced by irradiated (IR) and non-irradiated MBT-2/TGF-β(-) 3 were both significantly decreased when detected after in vitro culture for 48 hours. The result of flow cytometry analysis reveals that decreased production of TGF-β led to the increased expressions of MHC class I molecule and Fas on the surface of MBT-2 tumor cells. This finding may in part explain why the splenocytes obtained from day 17 tumor bearing mice (D17TBM) immunized with IRMBT-2/TGF-β(-) 3 on day 26 expressed a higher in vitro cytotoxic activity against MBT-2 tumor cells and hence ensured a better survival of D17TBM when they were rechallenged with a two-fold higher amount of wild-type MBT-2 tumor cells, 48 hours after surgical removal of the primary tumor. Our result implies that decreasing the amount of TGF-β secreted from the autologous tumor vaccine by antisense strategy may significantly improve its immunogenicity through up-regulation of both MHC class I and Fas expressions. Therefore, this could provide an alternative approach for future active immunotherapy.