Immunization with TGF-beta 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 effe ct of a transforming growth factor-beta (TGF-beta)-producing autologous tum or vaccine can be abrogated and I ender ed immunogenic by suppressing its T GF-beta secretion with antisense strategy. In this study, using a TGF-beta antisense gene modified MBT-2 tumor cell line [MBT-2/TGF-beta(-)#3] which w e established by ourselves, we first demonstrated that the amounts of TGF-b eta produced by irradiated (IR) and non-irradiated MBT-2/TGF-beta(-)#3 were both significantly decreased when detected after in vitro culture for 48 h ours. The result of flow cytometry analysis reveals that decreased producti on of TGF-beta 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) immuni zed with IRMBT-2/TGF-beta(-)#3 on day 26 expressed a higher in vitro cytoto xic 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 tum or Our result implies that decreasing the amount of TGF-beta secreted from the autologous tumor vaccine by antisense strategy may significantly improv e its immunogenicity through up-regulation of both MHC class I and Fas expr essions. Therefore, this could provide an alternative approach for future a ctive immunotherapy.