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BACKGROUND:: Interferon-γ (IFN-γ) gene/retroviral vector cell vaccinations have generated protective responses from unmodified tumor cell challenges as well as a regression of established tumors in animal models. The purpose of this trial was to determine the feasibility and safety of a direct intratumoral injection of IFN-γ retroviral vector in advanced melanoma patients. METHODS:: This was a phase I study, in which 13 patients received a single daily injection of a retroviral vector with the IFN-γ gene for 5 consecutive days (1.5 × 108 colony-forming units total dose); patients subsequently underwent resection of the injected lesion to confirm DNA transduction in situ. RESULTS:: No toxicity related to the injected vector was observed. Replication competent retrovirus was not observed in any prepared samples (n = 65). IFN-γ expression was confirmed in 3 of 10 harvested tumor samples; one was equivocal, and DNA transduction was unable to be confirmed by enzyme-linked immunospot assay in six samples. CONCLUSIONS:: An injection of IFN-γ gene/retroviral vector is well tolerated. DNA transduction was demonstrated in human subjects, confirming the feasibility of the direct injection approach for the gene therapy of solid tumors. Further trials to determine optimal schedule and potential efficacy are indicated. [ABSTRACT FROM AUTHOR]