Introduction and Objectives: TGF-β is a potent immunosuppressive cytokine produced by many tumor cells. Secretion of TGF-β by malignant cells may be a mechanism by which tumor cells escape destruction by tumor-specific T lymphocytes. In this study, we used a TGF-β producing C3H/He-MBT-2 murine bladder tumor model to investigate the feasibility of antisense oligonucleotide (ODN) gene therapy strategy to block the production of TGF-β from tumor cells and evaluate its influence on both in vitro tumor growth and in vivo tumor formation. Materials and Methods: Using a plasmid, pRUFCD, we constructed a recombinant plasmid pRUFCD/TGF-β1(-) containing antisense TGF-β ODN and then transfected it into MBT-2 cells by electroporation. Three transfectant clones were successfully obtained by their resistance to 5-fluorouracil and cytosine. Results: The secretion of TGF-β from the three obtained TGF-β antisense-blocked MBT-2 cell clones, as assessed by ELISA, were all decreased. Moreover, they all exhibited smaller colony size in the in vitro anchorage-independent soft agar colony forming assay. Tumor growths in mice injected with these three clones were all inhibited compared with those injected with parental tumor cells. Conclusion: This study demonstrates that after reducing the secretion of TGF-β1 on tumor cells by TGF-β1 antisense, ODN can inhibit their in vitro growth and in vivo tumor formation suggesting that this approach can be a potentially useful strategy to abolish the adverse immunosuppression effect of TGF-β1 producing autologous tumor vaccine and therefore to enhance host antitumor immune response.
|Number of pages||5|
|Issue number||3 A|
|Publication status||Published - 1998 May 1|
All Science Journal Classification (ASJC) codes
- Cancer Research