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Intratumoral injection of interferon-gamma gene-modified dendritic cells elicits potent antitumor effects: effective induction of tumor-specific CD8+ CTL response

Jianping Pan, Minghui Zhang, Jianli Wang, Qingqing Wang, Dajing Xia, Wenji Sun, Lihuang Zhang, Hai Yu, Xuetao Cao
Journal of Cancer Research and Clinical Oncology 2005, 131 (7): 468-78
15711825

PURPOSE: To examine the antitumor efficacy of intratumoral injection of interferon-gamma gene-modified dendritic cells (DC-IFN-gamma) in a B16 melanoma model and to investigate its related immunological mechanisms.

METHODS: C57BL/6 mice-derived DC were transfected with adenovirus encoding IFN-gamma or beta-galactosidase (DC-LacZ). Secretion of IFN-gamma and TNF-alpha by DC was detected by ELISA. Nitric oxide (NO) production was measured by Griess reaction. Cytotoxicity of DC against tumor cell lines and activity of cytotoxic T lymphocytes (CTLs) were determined by 51Cr-release assay. TRP-2aa180-188-specific CD8+ CTLs in tumor-bearing mice with different treatment were determined by ELISPOT.

RESULTS: DC-IFN-gamma could secrete high levels of IFN-gamma, NO and TNF-alpha. DC-IFN-gamma were cytolytic to B16 melanoma cells in vitro, but DC-LacZ and DC were not. Significant inhibition of tumor growth and prolonged survival were achieved in tumor-bearing mice intratumorally injected with DC-IFN-gamma when compared with those in tumor-bearing mice intratumorally injected with DC, DC-LacZ, fibroblasts, IFN-gamma gene-modified fibroblasts or PBS. After treatment with DC-IFN-gamma, enhanced Th1 and decreased Th2 responses were observed, and B16 melanoma antigen TRP-2aa180-188-specific CD8+ CTLs were induced significantly in the tumor-bearing mice.

CONCLUSIONS: Intratumorally injected DC-IFN-gamma can uptake tumor antigens in situ and cross-present tumor antigens to specific CD8+ T cells, hereby eliciting effective antitumor effects in murine model with preestablished B16 melanoma.

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