Membrane macrophage colony-stimulating factor on MADB106 breast cancer cells does not activate cytotoxic macrophages but immunizes rats against breast cancer

Weakly immunogenic, but highly malignant, rat MADB106 breast cancer cells w ere retrovirally transduced with the membrane form of macrophage colony-sti mulating factor (mM-CSF). The cloned mM-CSF-transfected MADB106 cells physi cally conjugated with macrophages, but were not killed by the macrophages i n 48-h cytotoxicity assays. Macrophages killed the mM-CSF-expressing tumors in the presence of noncytotoxic doses of either taxol or taxol plus cispla tin. This indicated that macrophages bind to the mM-CSF expressed on the tu mor cells, but for successful macrophage cytotoxicity to occur against mM-C SF-transduced tumor cells other factors must be present. The mM-CSF-transfe cted tumor cells were rejected when inoculated subcutaneously into normal r ats. Cloned MADB106 tumor cells which expressed high amount of mM-CSF were rejected, while tumor cells that displayed lower levels of mM-CSF grew in 6 0% of the inoculated rats. The mM-CSF-transfected tumors that grew were sma ller and had a greater amount of necrosis, compared to the viral vector tum ors. Rats that spontaneously rejected the mM-CSF-transfected MADB106 cells showed rechallenge resistance to unmodified parental MADB106 and R3230Ac br east cancers, but not to the F98 glioma. These observations suggest that br east cancer-specific immunity was induced by the inoculation of mM-CSF-expr essing MADB106 tumor cells.