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 MCA 106 tumor cells effectively protects the host from s ubsequent challenge with parental tumor. The same treatment fails to induce regression of established tumors, although tumor-specific CTL are generate d in the tumor-bearing animals. In contrast, a large tumor burden of the MC A106 fibrosarcoma can be successfully eliminated by treatment with MCA 106 tumor cells cotransduced with the B7.1 and gamma-IFN genes. Antitumor immun ity induced by the cotransductants is primarily dependent on CD8(+) T cells and partly on CD4(+) T cells and NK cells, and the enhanced therapeutic ef fect 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 vaccin es with a potent immunoprotective effect do not necessarily have therapeuti c potential and that weakly immunogenic tumors may be rendered highly immun ogenic by cotransfection with the genes for B7.1 and gamma-IFN.