Immunotherapy as a treatment for cancer has been intensely investigated, but few studies have resulted in meaningful clinical responses. Many fundamental principals of tumor immunology have been clarified in recent years with the recognition and description of many antigens in tumors that can be recognized by T lymphocytes. Vaccination strategies to induce an immune response against these tumor antigens have also been developed and shown to induce a T cell response in patients. However, studies showing an objective response of cancer regression following vaccination are limited in number. One explanation for this minimal response rate is that the immunogenicity of the vaccines used for these trials in humans is too low to induce a response of sufficient magnitude to result in cancer regression. The long-term goal of this project is to determine the utility of recombinant cytomegalovirus (rCMV)-based vaccines for systemic immunotherapy for cancer. Human CMV (hCMV) is a highly immunogenic virus that results in persistent, life-long infection in the human host. About half of the U.S. population has been exposed to hCMV infection as demonstrated by the finding of antibodies to defined viral epitopes in the serum (seropositive). The virus has unique characteristics as a vaccine including: 1) lack of disease associated with hCMV infection in the immune-normal host, 2) ability to re-infect hCMV-seropositive individuals, 3) large carrying capacity for heterologous DNA, 4) life-long persistence within the host corresponding to 5) induction of a large immune response (10-20% of both the CD4+ and CD8+ memory T cells directed against hCMV antigens in asymptomatically infected individuals). Such rCMV-based vaccines expressing defined heterologous target antigens are being developed and have promise as vaccines for infectious disease such as influenza and HIV. The purpose of this proposal is to extend these observations to determine the capacity of CMV-based vectors expressing cancer-associated target antigens as an immunotherapy for cancer.Immunotherapy as a treatment for cancer has been intensely investigated, but few studies have resulted in meaningful clinical responses. The purpose of this proposal is to determine the capacity of CMV-based vectors expressing cancer-associated target antigens as an immunotherapy for cancer. [unreadable] [unreadable] [unreadable]