Effect of GM-CSF and IL-2 co-expression on the anti-tumor immune response.
We evaluated the effect of potential therapeutic genes, GM-CSF and IL-2 respectively, or in combination of both cytokines, on the activation of systemic antitumor responses. CT26 tumor cells were modified to secrete GM-CSF and/or IL-2. The growth rate of the modified tumor cells versus the parental CT26 cells did not show any difference. When we implanted the CT26 tumor cells which secrete either GM-CSF or IL-2, delayed and suppressed tumorigenicity was observed. However, another CT26 cell line which expresses both GM-CSF and IL-2 (CT26/GMCSF/IL-2) did not form any tumor mass in the immunocompetent syngeneic Balb/c mice, showing the potential immune responses. Immunohistochemical examination of the modified tumor masses implanted with the cells expressing GM-CSF or IL-2 showed increased necrosis and infiltration of NK (CD56+) lineage cells and macrophage/monocytes. In the vaccination model, the growth of rechallenged wild-type CT26 was more suppressed int he mice which were injected with GM-CSF or IL-2, however, the wild-type CT26 tumor formed normal tumor mass in the mice vaccinated with CT26/GM-CSF/IL-2 showing acute non-T-cell mediated immune response. As a treatment, we injected those modified tumor cells into the established tumor. There we could find tumor growth suppression by the injection of cytokine-modified CT26 cells, especially by the CT26/GM-CSF/IL-2. In the present study we could induce the eradication of tumorigenicity by the transfection of both GM-CSF and IL-2 genes and a potent role in the growth suppression of an established tumor.
Lee
S G
SG
School of Biological Sciences, College of Natural Sciences, Seoul National University Hospital, Korea.
Heo
D S
DS
Yoon
S J
SJ
Jee
Y S
YS
Kang
J O
JO
Kim
K
K
Kim
C D
CD
Sung
M W
MW
Kim
N K
NK
D000818:Animals; D015152:Blotting, Northern; D015316:Genetic Therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000628:therapy*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor