Post immunity might well be an important mechanism by which malignant tumors can be contained or even destroyed by selected patients. The mechanisms by which tumors evade the immune system are most certainly varied and complex. Suboptimal expression of human histocompatibility antigens present on the surface of human tumor cells may prevent effective presentation of tumor specific antigens. The immune system could be relatively blind to the tumor cell, at least with regard to Class I MHC- restricted cytotoxic T lymphocytes. Retroviral vectors will be used to transfer the human gamma interferon gene into autologous tumor cells obtained from selected patients with metastatic melanoma. We will attempt to upregulate the expression of class I histocompatibility antigens and cellularly detectable tumor associated antigens by genetically transducing the cells with the gene for human gamma interferon. Also, the secreted gamma interferon should serve to activate an enhanced cytotoxic T-cell response. Short term tissue culture cells will be obtained from patients with more than one metastatic site. The cell cultures will be transduced with the gamma interferon-retroviral vector. After selection the cells will be briefly irradiated and will be utilized for subsequent serial immunizations. The study is designed to determine the safety, clinical response and biologic response (immune responses) in patients with metastatic melanoma who have failed other forms of therapy. The serially immunized patients will divide tumor samples, tumor infiltrating lymphocytes, and peripheral blood lymphocytes for in vitro studies designed to characterize the cell mediated immune response in the immunized patients. Appropriate clinical measurements will be completed in an effort to quantitate the potential therapeutic efficacy.
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