Murine interferon-alpha(1) gene-transduced ESb tumor cells are rejected byhost-mediated mechanisms despite resistance of the parental tumor to interferon-alpha/beta therapy

The highly metastatic ESb tumor is totally resistant to murine interferon-a lpha/beta (IFN-alpha/beta) therapy, regardless of the number of cells injec ted or the route of inoculation. In contrast, as we show herein, mouse IFN- alpha(1)-transduced ESb tumor cells were inhibited markedly when injected s ubcutaneously into immunocompetent mice. IFN-producing ESb tumor rejection was mediated by the immune system, because these tumor cells grew normally in immunosuppressed mice. Tumor regression was accompanied by extensive nec rosis and cellular infiltrates in the tumor area. These results further sup port the use of IFN-alpha in cytokine gene therapy of cancer and suggest th e advantage of using gene transfer rather than cytokine administration to e nhance an antitumor immune response.