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Annals of Surgical Oncology, Vol 6, Issue 2 186-194, Copyright © 1999 by Society of Surgical Oncology

ARTICLES

Interleukin-12 gene transfer results in CD8-dependent regression of murine CT26 liver tumors

S. M. Weber, F. Shi, C. Heise, T. Warner and D. M. Mahvi
Department of Surgery, University of Wisconsin School of Medicine, Madison, USA.

BACKGROUND: Interleukin (IL)-12 has potent antitumor effects in animal models. We hypothesized that direct transfer of the IL-12 gene to established tumors would result in tumor regression without significant toxicity. METHODS: Liver tumors were established by direct injection of CT26, a murine adenocarcinoma, into the livers of BALB/c mice, followed by three transfections with either murine IL-12, murine granulocyte-macrophage colony-stimulating factor, or luciferase cDNA using particle-mediated gene transfer. To assess the mechanism of this effect, immunohistochemical staining and depletion experiments with anti-CD4 or -CD8 antibodies were performed. RESULTS: Progressive growth of primary tumors and carcinomatosis were present by day 16 after transfection with luciferase or murine granulocyte-macrophage colony-stimulating factor. At 50 days, complete regression of tumor was evident in seven of eight IL-12-treated mice (P < .001). In IL-12-transfected livers, immunohistochemical staining revealed an increase in CD8+ T cells. Selective depletion of CD4+ or CD8+ T cells was performed before and during transfection with murine IL-12. At 50 days, 75% of control mice were tumor-free. Only 46% of CD4+ cell-depleted mice (P = .143) and 7% of CD8+ cell-depleted mice (P < .001) were tumor-free. CONCLUSIONS: IL-12 gene transfer using particle-mediated gene transfer results in complete regression of established CT26 liver tumors in 88% of mice; this effect is dependent on CD8+ T cells.


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