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Synergistic anti‐tumor effects with co‐expression of GM‐CSF and IFN‐γ in murine tumors
Author(s) -
Yoon Seong Jun,
Heo Dae Seog,
Kang Jung Ok,
Lee Sang Goo,
Kim Chun Dong,
Sung MyungWhun,
Kim Noe Kyeong
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980911)77:6<907::aid-ijc18>3.0.co;2-y
Subject(s) - cytokine , cancer research , tumor necrosis factor alpha , interferon gamma , immune system , immunology , interleukin 12 , cytotoxic t cell , biology , medicine , in vitro , biochemistry
We explored the potential therapeutic benefit of introducing GM‐CSF, IFN‐γ or a combination of both factors into CT26 tumor cells. CT26 cells secreting either GM‐CSF or IFN‐γ exhibited delayed tumorigenicity; however, cells expressing both GM‐CSF and IFN‐γ did not form tumors. Even when wild type CT26 cells were introduced into a distant site of mice that had been inoculated with CT26/GM‐CSF/IFN‐γ cells, no tumors were generated. Furthermore, when we injected GM‐CSF + IFN‐γ cells into animals bearing established tumors, the tumors were either rejected or their development was delayed, suggesting that synergistic effects were induced against these tumors via a systemic immune response. Histopathological examination of the tumors injected with cells expressing GM‐CSF and IFN‐γ combined showed necrosis and few signs of malignancy. The growth of tumors from mice treated with CT26/GM‐CSF/IFN‐γ cells exhibited a delay in tumor formation and no effects were seen in athymic nude mice, which are deficient in T lymphocytes, or in splenectomized nude mice, which are deficient in natural killer (NK) cells, respectively. Our data indicate a dual role for T and NK cells in mediating the anti‐tumor activity of this therapy. Our results suggest that transduction of tumor cells with both GM‐CSF + IFN‐γ results in a powerful synergistic effect of the 2 cytokines that is of greater therapeutic benefit than transduction with either cytokine alone. Int. J. Cancer 77:907–912, 1998.© 1998 Wiley‐Liss, Inc.