Journal
CANCER LETTERS
Volume 271, Issue 2, Pages 333-341Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2008.06.025
Keywords
Dendritic cell; Transforming growth factor-beta; Renal carcinoma; Vaccination; Cancer immunotherapy
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Funding
- Nature Science Foundation of China [30300413, 30672097]
- Technology Plan Emphasis Item of Peking [D0206011000091, 7072084]
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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 (T beta RIIDN) and thus made TGF-beta insensitive. Vaccination of the mice bearing Renca pulmonary metastases with the T beta RIIDN 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. (c) 2008 Elsevier Ireland Ltd. All rights reserved.
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