Therapeutic effect of recombinant plasmid-encoded human interleukin-12 in tumor-bearing mice

Abstract

The aim of this study was to investigate the effects of gene therapy using a recombinant plasmid encoding human interleukin-12 (rIL-12, pcDNA6-p70) on transplanted tumors in mice. Tumor-bearing mice were transplanted with sarcoma‑180 (S-180) cells and randomly divided into three groups of 10mice with each group receiving a separate treatment. Following this, pcDNA6-p70 (dissolved in purified water; 100µg/mouse), cyclophosphamide (dissolved in 0.9% saline; 40mg/kg) or 0.9%saline (100µl/mouse) was directly injected into the tumors on the 4th, 7th, 10th, 14th and 17th days following transplantation of the S-180 cells. Mice survival time was monitored and surviving mice were sacrificed on the 21st day. In addition to survival time, tumor volume, NK cell activity, spleen lymphocyte proliferation and IFN-γ production were investigated. The mice were also monitored for any adverse effects regarding the administration of pcDNA6-p70. Our results demonstrated that pcDNA6-p70 prolongs the survival time of tumor-bearing mice, decreases tumor size (P<0.01) and increases the proliferative response of spleen cells, the activity of NK cells and the serum level of IFN-γ. There were no significant adverse effects caused by the administration of pcDNA6-p70. The results of the present study support the hypothesis that gene therapy using the rIL-12 plasmid exerts a therapeutic effect in tumor models by triggering antitumor cellular immunity.