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 res pectively, or in combination of both cytokines, on the activation of system ic antitumor responses. CT26 tumor cells were modified to secrete GM-CSF an d/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 ce lls which secrete either GM-CSF or IL-2 delayed and suppressed tumorigenici ty was observed. However, another CT26 cell line which expresses both GM-CS F and IL-2 (CT26/ GMCSF/IL-2) did not form any tumor mass in the immunocomp etent syngeneic Balb/c mice, showing the potential immune responses. Immuno histochemical examination of the modified tumor masses implanted with the c ells expressing GM-CSF or IL-2 showed increased necrosis and infiltration o f NK (CD56+) lineage cells and macrophage/monocytes. In the vaccination mod el, the growth of rechallenged wild-type CT26 was more suppressed int he mi ce which were injected with GM-CSF or IL-5 however, the wild-type CT26 tnmo r formed normal tumor mass in the mice vaccinated with CT26/GM-CSF/IL-2 sho wing 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 th e 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.