Induction of antitumor immunity with combination of HER2/neu DNA vaccine and interleukin 2 gene-modified tumor vaccine

The therapeutic effects of both cytokine-secreting tumor vaccine and DNA va ccine were studied using mouse MBT-2 bladder cancer cells as a model. Cytok ine-secreting MBT-2, cells were obtained by infecting cells with retroviral particles containing interleukin (IL) 2-, IL-4-, or granulocyte-macrophage colony-stimulating factor (CM-CSF)-expression vector. The MBT-2-IL-2 cells were not tumorigenic in syngenic C3H mice at all. Tumor formation decrease d significantly for the MRT-2-GM-CSF cells, MBT-2-IL-2, -IL-4, and -GM-CSF cells were killed by irradiation and tested as tumor vaccines, The Irradiat ed MBT2-IL-2 cells could complete protect mice from the growth of the preex isting tumor cells, and the immune memory lasted for 8 months. On the other hand, irradiated MBT-2-IL-4 and MBT-2-GM-CSF cells were less effective. Wh en the loading tumor mass increased, all tunlor vaccines lost protective ef fects. DNA vaccine encoding the tumor antigen neu was additionally tested t o improve the therapeutic efficacy. Coinjection of 60 mug pSV-neu DNA was e ffective in enhancing the antitumor effects of MBT2-IL-2; however, DNA vacc ine alone cannot prevent the progression of the preexisting tumor. Immunohi stochemical analysis of tumor infiltrate revealed massive increase of CD4() lymphoid cells in the group of mice treated with both DNA vaccine and IL- 2-secreted tumor vaccine, Western blotting demonstrated the presence of ant i-neu antibody in the serum from immunized mice, In contrast, combination o f DNA vaccine and MBT-2-GM-CSF has no additive effect. The results indicate the combination of DNA vaccine and IL-2-secreting tumor vaccine can additi onally improve therapeutic efficacy, and the efficacy is correlated with th e increase of CD4(+) T lymphocytes and anti-neu antibody.