Efficient induction of local and systemic antitumor immune response by liposome-mediated intratumoral co-transfer of interleukin-2 gene and interleukin-6 gene

Interleukin 2 (IL-2) expressing plasmid and interleukin 6 (IL-6)-expressing plasmid were encapsulated in liposome and administrated intratumoraly into tumor-bearing mice 4 days after subcutaneous inoculation of B16F10 melanom a cells. The results showed that treatment of tumor-bearing mice with IL-2 gene or IL-6 gene transfer inhibited the growth of subcutaneous tumor and p rolonged the survival of tumor-bearing mice significantly when compared wit h the treatment of PBS or control gene transfer mediated by liposome (P<0.0 1). Combined transfer of IL-2 gene and IL-6 gene was found to elicit inhibi tory effects on the growth of B16F10 tumor more significantly and prolonged the survival period of tumor-bearing mice more obviously. We investigated the local immunity in tumor microenvironment and found that IL-2 and IL-6 g ene transfer could significantly increase the expression of lymphocyte func tion-associated antigen-1 on tumor infiltrating lymphocytes (TIL) and MHC-I molecule on tumor cells freshly isolated from the tumor mass. The NK and C TL activity of TIL increased markedly after the combined transfer of these two cytokine genes. We also observed the systemic antitumor immune response in the tumor-bearing mice and demonstrated that NK and CTL activity of spl enocytes and the production of IL-2, tumor necrosis factor and interferon-g amma from splenocytes increased obviously in mice after the combined transf er of IL-2 and IL-6 gene. In conclusion, local and systemic antitumor immun ity of the tumor-bearing host could be induced efficiently after the combin ed gene transfer. The enhanced specific and non-specific antitumor immunity might be responsible for the more potent antitumor effects of the combined gene therapy.