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Dendritic Cell Vaccine Therapy by Immunization with Fusion Cells of Interleukin‐2 Gene‐Transduced, Spleen‐Derived Dendritic Cells and Tumour Cells
Author(s) -
Ogawa F.,
Iinuma H.,
Okinaga K.
Publication year - 2004
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.0300-9475.2004.01411.x
Subject(s) - ctl* , spleen , cancer research , fusion gene , cytotoxic t cell , genetic enhancement , immunology , interleukin 12 , dendritic cell , immunotherapy , medicine , biology , immune system , cd8 , gene , biochemistry , in vitro
We examined the preventive and therapeutic effects of fusion cells prepared from spleen‐derived dendritic cells (DCs) transduced with the interleukin‐2 (IL‐2) gene and QRsP fibrosarcoma cells in a mouse lung metastasis model. The IL‐2 or LacZ gene was introduced into spleen‐derived DCs using an adenoviral vector. Irradiated QRsP tumour cells were fused with IL‐2 gene‐transduced DCs (fusion/IL‐2) or LacZ gene‐transduced DCs (fusion/LacZ) by polyethylene glycol. These fusion cells expressed major histocompatibility complexes (MHC) class I and II, CD86, CD11c and CD8α. Splenocytes from mice vaccinated with fusion cells showed increased production of interferon‐γ (IFN‐γ) and cytotoxic T‐lymphocyte (CTL) activity as compared with those vaccinated with DCs or tumour cells alone, and CTL levels were higher in fusion/IL‐2‐vaccinated mice than in fusion/LacZ‐vaccinated mice. In our experiments on the protective and therapeutic effects on lung metastasis, mice vaccinated with fusion/IL‐2 fusion/LacZ or fusion showed a significant reduction in pulmonary metastasis compared with those given DCs, tumour or phosphate‐buffered saline. The introduction of the IL‐2 gene into fusion cells produced more potent preventive and therapeutic effects. These results suggest that immunization with fusion cells prepared from spleen‐derived DCs and tumour cells is capable of inducing preventive and therapeutic anti‐tumour immunity against lung metastasis, and modification by the IL‐2 gene may increase anti‐tumour efficacy.