[Treatment of murine Lewis lung cancer with recombinant interleukin-12]

Abstract

Background & objective: Interleukin-12 (IL-12) is a proinflammatory cytokine with antitumor activity. The study was to compare the therapeutic effects of recombinant murine interleukin-12 (mIL-12) plasmid [pcDNA3.1(+)-mIL-12] and Lewis lung carcinoma (LLC) cell line which could stably express mIL-12 gene in LLC.

Methods: The recombinant plasmid was transfected into LLC cells with lipofectin to obtain LLC/mIL-12 cells which stably express mIL-12 gene. Tumors were established on the right hind leg of C57 BL/6 mice by the subcutaneous injection of 2 x 106 LLC cells. Then all mice were divided into 4 groups (n=10) randomly when the tumors reached 0.5-1.0 cm in diameter. Subsequently, the mice were treated by intratumor injection of pcDNA3.1(+)-mIL-12 plasmid or LLC/mIL-12 vaccine on the first, fourth, and seventh days. Tumor size was measured before and after treatment. Tumor growth curve, CTL and NK activity of spleen cells, and tumor lymphocyte infiltration were observed after all mice were killed on the fourteenth day.

Results: Tumor growth were inhibited in mice treated with pcDNA3.1(+)-mIL-12 plasmid or LLC/mIL-12 vaccine; the NK and CTL cell activity was augmented by mIL-12. Overall, the effects were more satisfactory in vaccine group than in plasmid group. There was abundant CD4+ and CD8+ T lymphocyte infiltration observed in both groups.

Conclusion: mIL-12 in LLC cell line can increase NK cells and CTL. Antitumor immune response could be induced both by pcDNA3.1(+)-mIL-12 plasmid and by LLC/mIL-12 vaccine; the latter one could induce stronger response.