Gene therapy with IL-12 induced enhanced anti-tumor activity in fibrosarcoma mouse model

Artif Cells Nanomed Biotechnol. 2016 Dec;44(8):1988-1993. doi: 10.3109/21691401.2015.1129618. Epub 2016 Jan 13.

Abstract

Context Immunotherapy is among the most promising modalities for treatment of cancer. Recently, interleukin 12 (IL-12) has been used as an immunotherapeutic agent in cancer gene therapy. IL-12 can activate dendritic cells (DCs) and boost anti-tumor immune responses. Objective In the current study, we have investigated if IL-12 gene therapy can lead to the regression of tumor mass in a mouse model of fibrosarcoma. Material and methods To investigate the therapeutic efficacy of IL-12, WEHI-164 tumor cells were transfected with murine-IL12 plasmids using Lipofectamine. Enzyme linked immunosorbent assay (ELISA) was used to confirm IL-12 expression in transfected cells. The fibrosarcoma mouse model was established by subcutaneous injection of transfected cells to Balb/C mice. Mice were sacrificed and the tumors were extracted. Tumor sizes were measured by caliper. The expression of IL-12 and IFN-γ was studied with real-time PCR and western blotting. The expression of Ki-67(a tumor proliferation marker) in tumor mass was studied by immunohistochemistry staining. Results and discussion The group treated with IL-12 showed a significant decrease in tumor mass volume (P: 0.000). The results of real-time PCR and western blotting showed that IL-12 and IFN-γ expression increased in the group treated with IL-12 (relative expression of IL-12: 1.9 and relative expression of IFN-γ: 1.766). Immunohistochemistry staining showed that Ki-67 expression was reduced in the group treated with IL-12. Conclusion IL-12 gene therapy successfully led to regress of tumor mass in the fibrosarcoma mouse model. This may serve as a candidate therapeutic approach for treatment of cancer.

Keywords: Gene therapy; IL-12; in vivo; tumor.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Female
  • Fibrosarcoma* / genetics
  • Fibrosarcoma* / metabolism
  • Fibrosarcoma* / pathology
  • Fibrosarcoma* / therapy
  • Genetic Therapy*
  • Interleukin-12* / biosynthesis
  • Interleukin-12* / genetics
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms, Experimental* / genetics
  • Neoplasms, Experimental* / metabolism
  • Neoplasms, Experimental* / pathology
  • Neoplasms, Experimental* / therapy

Substances

  • Interleukin-12