Synergistic anti-tumor effects with co-expression of GM-CSF and IFN-γ in murine tumors

✍ Scribed by Seong Jun Yoon; Dae Seog Heo; Jung Ok Kang; Sang Goo Lee; Chun Dong Kim; Myung-Whun Sung; Noe Kyeong Kim

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: French
• Weight: 385 KB
• Volume: 77
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19980911)77:6<907::aid-ijc18>3.0.co;2-y

✦ Synopsis

We explored the potential therapeutic benefit of introducing GM-CSF, IFN-␥ or a combination of both factors into CT26 tumor cells. CT26 cells secreting either GM-CSF or IFN-␥ exhibited delayed tumorigenicity; however, cells expressing both GM-CSF and IFN-␥ 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-␥ cells, no tumors were generated. Furthermore, when we injected GM-CSF ؉ IFN-␥ 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-␥ combined showed necrosis and few signs of malignancy. The growth of tumors from mice treated with CT26/GM-CSF/IFN-␥ 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-␥ results in a powerful synergistic effect of the 2 cytokines that is of greater therapeutic benefit than transduction with either cytokine alone.