Vaccination with transforming growth factor-beta insensitive dendritic cells suppresses pulmonary metastases of renal carcinoma in mice

Abstract: Dendritic cells (DCs) have been widely used as cancer vaccines. However, their functional abilities have often been suppressed by tumor-secreted immunosuppressants such as transforming growth factor-beta (TGF-β). We developed a new strategy using a TGF-β insensitive DC as cancer vaccine. The effect of this vaccine was tested in a murine pulmonary metastases model of renal carcinoma (Renca). Tumor lysate-pulsed DCs (TP-DCs) were infected with retrovirus containing gene of dominant negative TGF-β type II receptor (TβRIIDN) and thus made TGF-β insensitive. Vaccination of the mice bearing Renca pulmonary metastases with the TβRIIDN TP-DC induced powerful tumor-specific cytotoxic T lymphocyte (CTL) responses, suppressed pulmonary metastases, and prolonged survival times. These results suggest TGF-β-insensitive TP-DC vaccine can be used to enhance the antitumor efficacy of DC vaccine. [Copyright &y& Elsevier]