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

PMID: 18675506
Journal: Cancer letters (volume: 271, issue: 2, Cancer Lett. 2008 Nov;271(2):333-41)
Published: 2008-11-28

Tian F, Wang L, Qin W, Wang F, Song B, Li Y, Wen W, Zhang Z, Zhu K, Zhang Q, Lee C, Zhong W, Guo Y, Wang H


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-beta). We developed a new strategy using a TGF-beta 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-beta type II receptor (TbetaRIIDN) and thus made TGF-beta insensitive. Vaccination of the mice bearing Renca pulmonary metastases with the TbetaRIIDN TP-DC induced powerful tumor-specific cytotoxic T lymphocyte (CTL) responses, suppressed pulmonary metastases, and prolonged survival times. These results suggest TGF-beta-insensitive TP-DC vaccine can be used to enhance the antitumor efficacy of DC vaccine.