Tumour prevention and rejection with recombinant vaccinia

Abstract

Tumour-specific antigens (TSA; ref. 1) have been exploited in the diagnosis2 and imaging3 of human cancer and anti-TSA antibodies have therapeutic potential4. Vaccination with TSA5-8 or antiidiotypic (TSA) antibodies9,10 has also been used to control tumour growth in model systems. An effective immune response nevertheless demands copresentation of antigen with host histocompatibility determinants11. 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 postulated12-14. Tumorigenesis involves expression of three early PY proteins15-17, 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.