Tumor cells cotransduced with B7.1 and gamma-IFN induce effective rejection of established parental tumor.
Genetic modification of tumor cells with the gene for the B7.1 or with the genes for cytokines results in increased tumor cell immunogenicity. In the work reported here, immunization of naive animals with either B7.1 or gamma-IFN gene-modified MCA106 tumor cells effectively protects the host from subsequent challenge with parental tumor. The same treatment fails to induce regression of established tumors, although tumor-specific CTL are generated in the tumor-bearing animals. In contrast, a large tumor burden of the MCA106 fibrosarcoma can be successfully eliminated by treatment with MCA106 tumor cells cotransduced with the B7.1 and gamma-IFN genes. Antitumor immunity induced by the cotransductants is primarily dependent on CD8+ T cells and partly on CD4+ T cells and NK cells, and the enhanced therapeutic effect may be attributed to the in vivo increase of CTL precursors following treatment. The gamma-IFN and B7.1 genes must be expressed on the same tumor cell for optimal therapeutic effect. Our results suggest that tumor vaccines with a potent immunoprotective effect do not necessarily have therapeutic potential and that weakly immunogenic tumors may be rendered highly immunogenic by cotransfection with the genes for B7.1 and gamma-IFN.
Yang
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Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Vervaert
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Seigler
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HF
Darrow
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TL
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D007371:Interferon-gamma / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D009369:Neoplasms / Q000628:therapy*; D012190:Retroviridae; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D007371:Interferon-gamma