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

To enhance the antitumor immunity induced by IL-2 gene-modified tumor vacci ne, we proposed a combined protocol to treat tumor-bearing mice using IL-2 gene-modified tumor vaccine in combination with IL-I and low-dose Cyclophos phamide(Cy). After treatment with IL-2 gene-modified B16 melanoma cell vacc ine alone, the pulmonary metastases of tumor-bearing mice were reduced and their survival ti me was prolonged. The anti -metastases effect was improve d when the vaccine was used in combination with IL-1 or low-dose Cy. The be st 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, N K, and the levels of IL-2, TNF secreted by splenocytes increased after tumo r-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 gene-modified tumor vacci ne. These results demonstrated that the IL-2 gene modified vaccine could ex ert more potent anti-metastases effects when it is combined with IL-1 or/an d low-dose Cy by activating the specific and nonspecific antitumor immune r esponses more effectively.