Immunotherapeutic studies of different clonal lines of herpesvirus-induced fibrosarcoma in a syngeneic rat.

Transformation of White Buffalo rat embryonic cells by dye-light-inactivated herpesvirus type 2 resulted in the development of two clones of transformed cells (G2 and rat fibrosarcoma) with significantly different tumorigenic capabilities. The G2 cell line was initially nontumorigenic, while the rat fibrosarcoma line was very highly tumorigenic in rats. These significant differences in transformed cell clones from the same initial culture offered an opportunity to study aspects of the immunobiology of oncogenicity. The development of fibrosarcomas in immunoincompetent nude mice with the same early passages of the G2 cell line which were nontumorigenic in the immunocompetent rat suggested that immunologic resistance developed more effectively in the competent host against the G2 line than against rat fibrosarcoma cells. Syngeneic rats which were first exposed to the early passage nontumorigenic G2 cells were completely protected against tumor development by the rat fibrosarcoma cell lines. In subsequent in vitro passages of the G2 cell line, it lost its ability to protect against rat fibrosarcoma challenge and gradually became oncogenic in rats. Modification of antigenic exposure, accomplished by treating the G2 cells with cholesteryl hemisuccinate, resulted in an increase in the protection by these cells and a delay in tumor development.