Exp Mol Med.
1997 Mar;29(1):53-58.
Retroviral-mediated IL-12 gene therapy for advanced murine tumors
- Affiliations
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- 1SEOUL NATL UNIV, INST MOL BIOL & GENET, SEOUL 151742, SOUTH KOREA.
- 2SEOUL NATL UNIV, DEPT BIOL, SEOUL 151742, SOUTH KOREA.
- 3UNIV PITTSBURGH, SCH MED, DEPT SURG, PITTSBURGH, PA, 15261.
- 4UNIV PITTSBURGH, SCH MED, DEPT MOL GENET & BIOCHEM, PITTSBURGH, PA, 15261.
- 5SAMSUNG MED CTR, DIV HEMATOL ONCOL, SEOUL 135230, SOUTH KOREA.
Abstract
- Interleukin 12 (IL-12), a heterodimeric cytokine, promotes an effective antitumor response against tumors of various histological types when delivered systemically as a protein or locally by gene transfer. We investigated parameters that influenced the effectiveness of IL-12 retroviral-mediated gene therapy of cancer in animals using the murine breast cancer line TS/A. Syngeneic fibroblasts (TIB80), stably transduced with a retrovirus expressing murine IL-12, were used for peritumoral injection. Injection of fibroblasts into established tumors resulted in complete regression of tumor in 40 % of animals in a dose dependent manner when treated on day 4, and 20 % when treated on day 8. Significant inhibition of growth of day 21 and day 40 tumors was observed following peritumoral injection of IL-12-expressing fibroblasts in a dose-dependent manner. Delivery of IL-12 by syngeneic fibroblasts at a tumor site is effective in eradicating established, weakly immunogenic TS/A tumors.
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