ALIEN GENE TRANSFECTION IN THE THERAPY OF METASTASES

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The goal of these investigations is to develop and use genetically engineered murine tumor cells for the treatment of established metastases. The rationale for these studies is based on the hypothesis that tumor cells express "hapten-like" antigens that are poorly immunogenic but remain antigenic in that they can be recognized by an engendered immune response. The transfection and expression of a strong viral antigen such as hemagglutinin (HA) provides a basis for "associative recognition", where a response to HA fosters a response to the tumor associated antigen (TAA). This point has been proven using three different murine tumors which when transfected with, and expressing HA, protect against a challenge with non- transfected parent cells. A second goal of these studies is to transfect murine tumors with genes coding for lymphokines such as IL_2 and IL-4, or IFN-gamma. These new cell lines will allow us to address the role of delayed type hypersensitivity (65kDa) and MHC Class I expression (IFN- gamma), in tumor rejection. They will also allow us to determine more conclusively if bypassing T-cell help accelerates the immune response (IL- 4). Our ultimate goal is to use these genetically engineered cells, or combinations thereof, to treat established metastases in mice.