Recombinant polyoma--vaccinia viruses: T antigen expression vectors and anti-tumor immunization agents

Live vaccinia virus recombinants expressing viral antigens have recently been developed as effective anti-viral vaccines. We have examined the possibility of extending this approach to specific anti-tumor immunity, using tumors induced by the polyoma virus (PyV) as a model system. Three recombinant vaccinia viruses, separately encoding the three early proteins of the polyoma virus (large, middle and small tumor (T) antigens) were constructed. Each recombinant efficiently expresses the appropriate T antigen, which exhibits biochemical properties and subcellular localization of the authentic PyV protein. The potential of the recombinants to elicit immunity towards PyV-induced tumors was assessed in rats by a challenge injection of syngeneic PyV-transformed cells. After prior immunization with the large-T or the middle-T viruses, small tumors developed, which later regressed and were eliminated in more than 50% of the animals. In contrast, the small-T virus failed to elicit tumor rejection. Established tumors could also be eliminated by curative vaccinations. No circulating antibodies directed against PyV large-T or middle-T antigens were detected in animals vaccinated with the large-T or middle-T viruses, suggesting that rejection may be due to a cell-mediated immune response.