Construction and characterization of a triple-recombinant vaccinia virus encoding B7-1, interleukin 12, and a model tumor

serve as vaccines for the treatment of experimental murine tumors has recently been achieved. The cooperative effects of immune system modulators, including cytokines such as interleukin 12 (IL-12) and costimulatory molecules such as B7-1, may be necessary for activation of cytotoxic T lympho-cytes. Thus, we have explored the feasibility and the efficacy of inclusion of these immunomodulatory molecules in recom-binant virus vaccines in an experimental antitumor model in mice that uses Escherichia coli b-galactosidase as a target antigen. Methods: We developed a ‘‘cassette’ ’ system in which three loci of the vaccinia virus genome were used for homologous recombination. A variety of recombinant vac-cinia viruses were constructed, including one virus, vB7/b/ IL-12, that contains the following five transgenes: murine B7-1, murine IL-12 subunit p35, murine IL-12 subunit p40