[Treatment of spontaneous metastatic lung cancer with tumor antigen-pulsed, interleukin-18 gene-modified dendritic cells].

OBJECTIVE

To investigate the effect of tumor antigen-pulsed, interleukin-18 (IL-18) gene-modified dendritic cells in treatment of spontaneous metastatic lung cancer.

METHODS

3LL Lewis lung cancer cells were injected into the footpads of C57BL/6 mice to establish a spontaneous metastatic lung cancer model. Ninety-six mice with lung cancer were divided into 8 groups, 12 in each. treated differently. One group was treated by subcutaneous vaccination for two times of tumor antigen peptide Mut1-pulsed, IL-18 gene-modified dendritic cells (DC-IL-18/Mut1) that were derived from normal bone marrow. The other groups were treated with other measures. After treatment, the lung weight, number of metastatic nodes on the lung surface, survival time, and NK and CTL activities were examined.

RESULTS

Compared with the mice treated with Mut1-pulsed control LacZ gene-modified DC and those treated with untreated DC, the tumor-bearing mice treated with DC-IL-18/Mut1 had the lightest lung weight (215 mg +/- 20 mg Vs 398 mg +/- 23 mg and 987 mg +/- 45 mg, t = 14.7 and 38.4, P < 0.01), the least lung metastatic nodes (0 Vs 7.8 +/- 2.7 and 49, P < 0.01), the longest survival time (chi(2) = 6.78 and 10.49 respectively, P < 0.01), the strongest cytotoxic T cell activity (53.4 +/- 3.1 Vs 41.3 +/- 2.6 and 9.8 +/- 2.1, t = 13.4 and 15, 7 respectively, P < 0.01), and increased proportions of CD4 + Tcells, CD8 + Tcells, and NK cells.

CONCLUSION

Tumor antigen-pulsed, IL-18 gene-modified dendritic cells have a significant therapeutic effect on spontaneous netastatic lung cancer through induction of anti-tumor immunological responses.