The gene encoding the large-T protein of polyoma virus (plt), the E1A genes of adenoviruses, the viral myc gene (v-myc) or rearranged forms of the cellular c-myc gene confer on rat embryo fibroblast (REF) cells in primary culture a series of new properties ('immortality', reduced serum requirement and sensitivity to transformation by viral and activated cellular oncogenes) but do not induce the appearance of transformed foci. We now report that focus formation can be induced after transfer of these genes into either REF or established FR3T3 rat cells by subsequent exposure to the tumour promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). Frequencies of transformation are in the same range as those usually observed for transformation with complete polyoma DNA or with a mixture of cloned myc and ras oncogenes. These results further characterize the 'immortalized' state induced by plt and myc as one in which the cells maintain a normal growth control in many respects but can be further acted upon to produce a neoplastic progeny.

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Tumour prevention and rejection with recombinant vaccinia.

Tumour-specific antigens (TSA; ref. 1) have been exploited in the diagnosis and imaging of human cancer and anti-TSA antibodies have therapeutic potential. Vaccination with TSA or anti-idiotypic (TSA) antibodies has also been used to control tumour growth in model systems. An effective immune response nevertheless demands copresentation of antigen with host histocompatibility determinants. We therefore examined whether live vaccinia virus recombinants expressing TSA in cells of the vaccinated host might better elicit tumour immunity. Polyoma virus (PY) is tumorigenic in rodents; because killed PY-transformed cells can elicit tumour immunity, a PY-specific TSA has been postulated. Tumorigenesis involves expression of three early PY proteins, large-T (LT), middle-T (MT) and small-T (ST), but their role as TSAs is unclear. We therefore expressed the three T proteins in separate vaccinia recombinants. Rejection of PY tumours was observed in rats immunized with recombinants expressing either LT or MT. Further, tumour-bearing animals could be induced to reject their tumours by inoculation of recombinants.

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[Polyoma virus mutants].

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Cell Transformation, Neoplastic↗