Retroviral vector-mediated gamma-interferon gene transfer into tumor cells generates potent and long lasting antitumor immunity.
Retroviral vectors were used to introduce the gamma-interferon (IFN-gamma) gene into CMS-5 cells, a weakly immunogenic tumor of BALB/c origin. After selection in G418-containing medium, colonies were isolated, cloned, and expanded to cell lines. IFN-gamma secretion was assessed using a bioassay and enzyme-linked immunosorbent assay, and high (25 units/ml) and low (5 units/ml) IFN-gamma producers were isolated. Tumor growth was followed after intradermal injection, and spleen cells were isolated at different time points. IFN-gamma secretion by tumor cells abrogated their tumorigenicity and induced a persistent and specific antitumor immunity. In contrast to the normally observed cellular immunosuppression in unmodified CMS-5 tumor-bearing mice, IFN-gamma-producing tumors induced a long lasting state of T-cell immunity, as judged by rejection of a CMS-5 tumor challenge and persistence of specific cytotoxic activity in the spleen cell population. High levels of tumor-specific cytotoxic activity could also be detected if IFN-gamma-secreting tumor cells, but not unmodified CMS-5 cells, were used as targets at a time point when immunosuppression was usually seen. These studies highlight the potential advantages of localized IFN-gamma secretion to induce potent antitumor immune responses.
Gansbacher
B
B
Department of Hematology/Lymphoma, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Bannerji
R
R
Daniels
B
B
Zier
K
K
Cronin
K
K
Gilboa
E
E
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D004247:DNA / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005354:Fibrosarcoma / Q000276:immunology* / Q000473:pathology; D005822:Genetic Vectors; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008979:Moloney murine leukemia virus / Q000235:genetics*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D014162:Transfection
D007371:Interferon-gamma; D004247:DNA