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-Interferon Gene Transfer into Tumor Cells Generates Potent and Long Lasting Antitumor Immunity1
Departments of Hematology/Lymphoma [B. G.] and Molecular Biology [R. B., B. D., K. C., E. G.], Memorial Sloan-Kettering Cancer Center, New York, New York 10021, and Departments of Medicine and Microbiology, Mt. Sinai Medical Center, New York, New York 10029 [K. Z.]
Retroviral vectors were used to introduce the 
-interferon (IFN-) 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- secretion was assessed using a bioassay and enzyme-linked immunosorbent assay, and high (25 units/ml) and low (5 units/ml) IFN- producers were isolated. Tumor growth was followed after intradermal injection, and spleen cells were isolated at different time points. IFN- 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--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--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- secretion to induce potent antitumor immune responses.
1 This project was supported by a grant from the Schultz Foundation and the Special Projects Committee Award from the Memorial Sloan-Kettering Cancer Center Society (B. G.) and the Kleberg Foundation and Memorial Sloan-Kettering Cancer Center Society (E. G.).
2 To whom requests for reprints should be addressed.
Received 7/ 5/90. Accepted 9/14/90.
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