Enhanced antitumor immune responses of IL-2 gene-modified tumor vaccine by combination with IL-1 and low dose cyclophosphamide.

To enhance the antitumor immunity induced by IL-2 gene-modified tumor vaccine, we proposed a combined protocol to treat tumor-bearing mice using IL-2 gene-modified tumor vaccine in combination with IL-1 and low-dose Cyclophosphamide(Cy). After treatment with IL-2 gene-modified B16 melanoma cell vaccine alone, the pulmonary metastases of tumor-bearing mice were reduced and their survival time was prolonged. The anti-metastases effect was improved when the vaccine was used in combination with IL-1 or low-dose Cy. The best therapeutic effect was achieved when the IL-2 gene-modified vaccine was combined with IL-1 and low-dose Cy. The cytotoxicity of the splenic CTL, NK, and the levels of IL-2, TNF secreted by splenocytes increased after tumor-bearing mice were treated with the IL-2 gene-modified tumor vaccine. The above antitumor immune functions were augmented more significantly when IL-1, low-dose Cy were used in combination with IL-2 genemodified tumor vaccine. These results demonstrated that the IL-2 gene modified vaccine could exert more potent anti-metastases effects when it is combined with IL-1 or/and low-dose Cy by activating the specific and non-specific antitumor immune responses more effectively.