Admixture of a Recombinant Vaccinia Virus Containing the Gene for the Costimulatory Molecule B7 and a Recombinant Vaccinia Virus Containing a Tumor-associated Antigen Gene Results in Enhanced Specific T-Cell Responses and Antitumor Immunity

摘要: At least two signals are required for the activation of naive T cells by antigen-bearing target cells: an antigen-specific signal, delivered through T-cell receptor, and a costimulatory signal surface molecule CD28 its natural ligand B7-1. The immunological benefit coexpression B7 with antigen has been demonstrated use several retroviral systems to transfect cells. Although engineering recombinant constructs genes or more antigens can mediate dual expression those antigens, disadvantages this approach include time construction each desirable combination inability control differential levels gene product. An alternative would utilize separate that could be admixed appropriately before administration. In report we describe functional consequences admixture vaccinia murine B7-1 (rV-B7) expressing human carcinoembryonic (rV-CEA). Coinfection resulted in high cell both CEA molecules. Immunization mice various ratios (1:3, 1:1, 3:1) rV-CEA rV-B7 at 3:1 ratio generation optimal CEA-specific responses. Next, examined efficacy on antitumor activity. Typically, injection carcinoma leads death host. One immunization C57BL/6 rV-CEA:rV-B7 (3:1) no tumor establishment. contrast, administration alone had little effects. These studies demonstrate advantages viruses deliver molecules tumor-associated antigen. availability single construct ability alter also have potential utility when coinfecting containing infectious agents other genes.