Phase I trial of interferon-gamma (IFN-gamma) retroviral vector administered intratumorally to patients with metastatic melanoma

Background: Interferon-gamma (IFN-gamma) gene/retroviral vector cell vaccin ations have generated protective responses from unmodified tumor cell chall enges as well as a regression of established tumors in animal models. The p urpose of this trial was to determine the feasibility and safety of a direc t intratumoral injection of IFN-gamma retroviral vector in advanced melanom a patients. Methods: This was a phase I study, in which 13 patients received a single d aily injection of a retroviral vector with the IFN-gamma gene for 5 consecu tive days (1.5 x 10(8) colony-forming units total dose); patients subsequen tly underwent resection of the injected lesion to confirm DNA transduction in situ. Results: No toxicity related to the injected vector was observed. Replicati on competent retrovirus was not observed in any prepared samples (n = 65). IFN-gamma expression was confirmed in 3 of 10 harvested tumor samples; one was equivocal, and DNA transduction was unable to be confirmed by enzyme-li nked immunospot assay in six samples. Conclusions: An injection of IFN-gamma gene/retroviral vector is well toler ated. DNA transduction was demonstrated in human subjects, confirming the f easibility of the direct injection approach for the gene therapy of solid t umors. Further trials to determine optimal schedule and potential efficacy are indicated.