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

Ann Surg Oncol. 1999 Mar;6(2):186-94. doi: 10.1007/s10434-999-0186-1.


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.

MeSH terms

  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Animals
  • CD4 Antigens
  • CD4-Positive T-Lymphocytes
  • CD8 Antigens
  • CD8-Positive T-Lymphocytes
  • DNA, Complementary
  • Gene Transfer Techniques*
  • Genetic Therapy* / methods
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Immunohistochemistry
  • Immunotherapy / methods
  • Interleukin-12 / genetics*
  • Interleukin-12 / therapeutic use
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Luciferases
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Plasmids
  • Transfection
  • Tumor Cells, Cultured


  • CD4 Antigens
  • CD8 Antigens
  • DNA, Complementary
  • Interleukin-12
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Luciferases