It has been shown that a variety of human and animal cancers escape immune surveillance by decreasing their major histocompatibility complex (MHC) Class I gene expression. The under-representation of HLA antigens in human tumors is usually associated with a poor prognosis. Further, it has been shown that the introduction into tumors of vectors able to drive high expression of Class I genes, or the induction of Class I antigens in tumors by agents such as viruses or IFNs, can prove therapeutic. This novel approach might become a great benefit to cancer patients, one which might be achievable through gene therapy. However, for safety reasons as well as to minimize systemic toxicities, it is important to make such approaches as targeted as possible. The objectives of this proposal are: 1) to identify and characterize both the cellular and viral components responsible for the increased transcriptional activity of certain MHC gene(s) following viral infection, 2) to transfer these components as well as MHC genes proper into human tumor cells via targetable gene therapy vectors recently developed, and 3) to determine the potential therapeutic value of this strategy in animal models.
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