Reduction of tumorigenicity by an interferon-gamma-gene-transduced tumor on another syngeneic tumor in a murine model.

To evaluate the effect of interferon-gamma-gene-transduced cells, DS mice were inoculated into their footpads with syngeneic mammary adenocarcinoma SC42 admixed with interferon-gamma producing mammary adenocarcinoma SC115Kgamma, which had been established by an interferon-gamma-gene transduction in another syngeneic mammary adenocarcinoma SC115 using retroviral vectors. These mice rejected both tumor cells and developed resistance to subsequent challenges with either SC115 or SC42 cells inoculated into their opposite posterior footpads. These results thus indicate that systemic immunological memory to each of the independent tumor cell lines developed in these mice. Although the SC42 cells admixed with irradiated SC115Kgamma cells were rejected by these mice, the SC42 cells admixed with irradiated SC115neoR, in which the neo-gene had been transduced, were observed to proliferate. Tumor rejection was reversed by an in vivo administration of anti-interferon-gamma antibody, thus suggesting that locally produced interferon-gamma plays an important role in tumor elimination and immunological memory induction. In conclusion, interferon-gamma-gene-transduced tumor cells are therefore considered to have a therapeutic potential for other types of malignant tumor cell lines.