Phase I trial of retroviral vector-mediated interferon (IFN)-gamma gene transfer into autologous tumor cells in patients with metastatic melanoma.

The purpose of this study was to determine the safety of treating melanoma patients with retroviral vector-mediated interferon (IFN)-gamma gene-transduced autologous tumor cells. We designed a phase I study, in which irradiated, autologous, transduced melanoma cells expressing the IFN-gamma gene were injected subcutaneously every 2 weeks with escalating cell doses for six injections. Tumor tissue was harvested from 58 patients with metastatic melanoma. Twelve patients had sufficient expansion of autologous tumor (0.56-160 x 10(7) cells) and adequate IFN-gamma expression after gene transduction (2-79,000 U/10(6) cells/24 hours) for injections. Five patients received injections. No toxicity was attributed to the IFN-gamma retroviral vector in the patients injected. One of the injected patients remains disease-free after 13 injections, following the surgical removal of brain, adrenal, and lung metastases. We found that injections of autologous tumor cells transduced by IFN-gamma gene were well tolerated. However, the ability to develop primary autologous melanoma cell lines was limited, and only a minority of patients were injected.