Synergistic anti-tumor effects with co-expression of GM-CSF and IFN-gamma in murine tumors.
We explored the potential therapeutic benefit of introducing GM-CSF, IFN-gamma or a combination of both factors into CT26 tumor cells. CT26 cells secreting either GM-CSF or IFN-gamma exhibited delayed tumorigenicity; however, cells expressing both GM-CSF and IFN-gamma 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-gamma cells, no tumors were generated. Furthermore, when we injected GM-CSF + IFN-gamma 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-gamma combined showed necrosis and few signs of malignancy. The growth of tumors from mice treated with CT26/GM-CSF/IFN-gamma 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-gamma results in a powerful synergistic effect of the 2 cytokines that is of greater therapeutic benefit than transduction with either cytokine alone.
Yoon
S J
SJ
Cancer Research Center, Seoul National University Medical College, Korea.
Heo
D S
DS
Kang
J O
JO
Lee
S G
SG
Kim
C D
CD
Sung
M W
MW
Kim
N K
NK
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015197:Carcinogenicity Tests; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C
D000970:Antineoplastic Agents; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor