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 mela noma patients with retroviral vector-mediated interferon (IFN)-gamma g ene-transduced autologous tumor cells. We designed a phase I study, in which irradiated, autologous, transduced melanoma cells expressing th e IFN-gamma gene were injected subcutaneously every 2 weeks with escal ating cell doses for six injections. Tumor tissue was harvested from 5 8 patients with metastatic melanoma. Twelve patients had sufficient ex pansion 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 ho urs) for injections. Five patients received injections. No toxicity wa s attributed to the IFN-gamma retroviral vector in the patients inject ed. One of the injected patients remains disease-free after 13 injecti ons, following the surgical removal of brain, adrenal, and lung metast ases. We found that injections of autologous tumor cells transduced by IFN-gamma gene were well tolerated. However, the ability to develop p rimary autologous melanoma cell lines was limited, and only a minority of patients were injected.