SUPPRESSION OF TUMORIGENICITY AND METASTASIS IN MURINE UV-2237 FIBROSARCOMA CELLS BY INFECTION WITH A RETROVIRAL VECTOR HARBORING THE INTERFERON-BETA GENE

In this study, we endeavored to determine the effectiveness of interfe ron beta (IFN beta) gene therapy against highly metastatic murine UV-2 237m fibrosarcoma cells. UV-2237m cells were engineered to produce mur ine IFN beta constitutively following infection by a retroviral vector harboring the murine IFN beta gene. Parental (UV-2237m-P), control-ve ctor-transduced (UV-2237m-Neo), and IFN beta-transduced (UV-2237m-IFN beta) cells were injected subcutaneously (s.c.) or intravenously (i.v. ) into syngeneic mice. Parental and control-transduced cells produced rapidly growing tumors, whereas IFN beta-transduced cells did not. The tumorigenicity of IFN beta-sensitive or -resistant parental cells was significantly suppressed when they were injected s.c. together with I FN beta-transduced cells. The IFN beta-transduced cells did not inhibi t growth of parental cells injected s.c. at a distant site. UV-2237m-I FN beta cells produced s.c. tumors in nude, SCID/Beige, and natural ki ller(NK)-cell-compromised syngeneic mice. The IFN beta-transduced cell s were more sensitive to in vitro splenic cell-mediated lysis than wer e the parental or control-transduced cells. Pretreatment of C3H/HeN mi ce with the NK-cell-selective antiserum (anti-asialoGM1) partially abr ogated the cytotoxic activity of the cells. Cytotoxic activity was not observed in mixed culture of UV-2237m-IFN beta cells and splenic cell s from SCID/Beige mice. Significant cytotoxicity against UV-2237m-IFN beta cells was mediated by macrophages activated by either IFN gamma, lipopolysaccharide, or a combination of both. Our data led us to concl ude that the constitutive expression of IFN beta can suppress tumorige nicity and metastasis of UV-2237m cells, which is due, in part, to act ivation of host effector cells.