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Mol Ther ; 3(2): 216-24, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11237678

ABSTRACT

Weakly immunogenic, but highly malignant, rat MADB106 breast cancer cells were retrovirally transduced with the membrane form of macrophage colony-stimulating factor (mM-CSF). The cloned mM-CSF-transfected MADB106 cells physically conjugated with macrophages, but were not killed by the macrophages in 48-h cytotoxicity assays. Macrophages killed the mM-CSF-expressing tumors in the presence of noncytotoxic doses of either taxol or taxol plus cisplatin. This indicated that macrophages bind to the mM-CSF expressed on the tumor cells, but for successful macrophage cytotoxicity to occur against mM-CSF-transduced tumor cells other factors must be present. The mM-CSF-transfected tumor cells were rejected when inoculated subcutaneously into normal rats. 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 60% of the inoculated rats. The mM-CSF-transfected tumors that grew were smaller and had a greater amount of necrosis, compared to the viral vector tumors. Rats that spontaneously rejected the mM-CSF-transfected MADB106 cells showed rechallenge resistance to unmodified parental MADB106 and R3230Ac breast cancers, but not to the F98 glioma. These observations suggest that breast cancer-specific immunity was induced by the inoculation of mM-CSF-expressing MADB106 tumor cells.


Subject(s)
Breast Neoplasms/immunology , Breast Neoplasms/prevention & control , Cancer Vaccines , Cell Membrane/metabolism , Macrophage Colony-Stimulating Factor/genetics , Macrophages/metabolism , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Bone Marrow Cells/cytology , Cisplatin/pharmacology , Cloning, Molecular , Female , Flow Cytometry , Glioma/immunology , Glioma/prevention & control , Immunohistochemistry , Macrophage Colony-Stimulating Factor/metabolism , Necrosis , Neoplasm Transplantation , Paclitaxel/pharmacology , Rats , Rats, Inbred F344 , Retroviridae/genetics , Time Factors , Transduction, Genetic , Transfection , Tumor Cells, Cultured
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