TNF-alpha gene-modified dendritic cells act as more potent adjuvants for peptide delivery to induce specific antitumor immunity in mice.
OBJECTIVE
To investigate the antitumor immune efficiency of mouse dendritic cells (mDCs) by using adenovirus-mediated tumor necrosis factor-alpha (AdV-TNF-alpha) gene transfer.


METHODS
MDCs infected with AdV-TNF-alpha and AdV-pLpA (no gene insert) at 100 multiplicity of infection (MOI) were analyzed by RNase protection assay for their cytokine secretion. Mixed lymphocyte reactions were also performed to analyze their capacity for alloantigen-presentation. C57BL/6 mice were challenged with R3LL tumor cells (Lewis lung carcinoma line) 10 days after vaccination with different engineered DCs and regular DCs as well.


RESULTS
Compared to AdV-pLpA and mock-infected DCs, AdV-TNF-alpha-infected DCs displayed up-regulated expression of alpha tumor necrosis factor, interleukin-12 (IL-12), interleukin-18 (IL-18) and granulocyte macrophage colony stimulation factor (GM-CSF), and indicated stronger allogeneic T cell proliferative responses. Furthermore, vaccination of mice with dendritic cell tumor necrosis factor-alpha (DCTNF-alpha) pulsed with Mut1 peptide induced more efficient tumor-specific cytotoxic T lymphocyte (CTL) cytotoxicity against R3LL tumor cells in vitro and with efficient antitumor immunity in vivo.


CONCLUSIONS
This type of engineered DCs could be applied in clinical settings of DC-based cancer vaccines.
Zhang
Weidong
W
Division of Microbiology, Department of Pathogenic Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Yang
Hong
H
Wang
Zehua
Z
Jim
Xiang
X
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha