ANTITUMOR-ACTIVITY OF 3 MOUSE MAMMARY-CANCER CELL-LINES AFTER INTERFERON-GAMMA GENE TRANSFECTION

Background. The antitumor effects of three mouse mammary tumors transf ected to express interferon-gamma were evaluated. Methods, Three immun ologically different tumors were used: DA3 EMT6, and 410. All three ce ll lines were successfully transfected with highly efficient viral vec tors. Wild type or transfected tumor cells were injected subcutaneousl y into Balb/c mice. Animals were observed for tumor growth and the ind uction of immunologic memory. Results. A significant decrease occurred in the size of all transfected tumors, EMT6 1.9 cm(2), DA3 1.7, and 4 10 1.8 compared with nontransfected control tumors with a mean size of 4 cm(2) on day 30. To further test the development of immunity, anima ls were injected with either nontransfected or transfected tumors and challenged with nontransfected tumor. Animals immunized with transfect ed tumor cells had significantly smaller tumors, EMT6 2.5 cm(2), DA3 3 .1, and 410 2.4 compared with controls with a mean size of 4 cm(2). No specific splenocyte cytotoxicity was shown. Expression of major histo compatibility complex class I antigens was enhanced in the 410 and DA3 tumor lines. Conclusions, Significant antitumor effects were observed after interferon-gamma gene transfection of three mouse mammary cance r cell lines. Up-regulation of major histocompatibility complex class I antigen expression is a partial explanation of these findings. These results provide preliminary studies for gene therapy of human breast cancer.