Vaccination with transforming growth factor-beta insensitive dendritic cells suppresses pulmonary metastases of renal carcinoma in mice.
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.
Tian
Feng
F
Department of Urology, Xijing Hospital, Fourth Military Medical University, 15 Chang Le West Road, Xi'an, Shaanxi Province 710032, China.
Wang
Longxin
L
Qin
Weijun
W
Wang
Fuli
F
Song
Bin
B
Li
Yu
Y
Wen
Weihong
W
Zhang
Zheng
Z
Zhu
Kaichang
K
Zhang
Qiang
Q
Lee
Chung
C
Zhong
Weide
W
Guo
Yinglu
Y
Wang
He
H
D000818:Animals; D015153:Blotting, Western; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology*; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology*
D016212:Transforming Growth Factor beta