PHASE-I STUDY TO THE IMMUNOTHERAPY OF METASTATIC MALIGNANT-MELANOMA BY A CANCER VACCINE CONSISTING OF AUTOLOGOUS CANCER-CELLS TRANSFECTED WITH THE HUMAN IL-2 GENE

The direct modification of tumor cells using cytokine genes as a strat egy to enhance host immunity against cancer has been studied extensive ly in animal models. Results obtained showed that mice injected with I L-7-transfected cancer cells mount a tumor-specific immune response th at is sufficient in magnitude to protect the animals against a challen ge with a tumorigenic dose of wild-type parental cancer cells. Current ly, trials are ongoing to determine the feasibility of such a treatmen t in patients with renal cell carcinoma, colon carcinoma and melanoma. We now propose a cancer vaccine trial for stage IV melanoma patients with no hope for cure by either chemotherapy, surgery or irradiation. The vaccine consists of irradiated, autologous melanoma cells which ha d been genetically engineered by means of receptor-mediated, adenoviru s-augmented gene delivery (transferrinfection) to produce human IL-2. Patients receive repeated injections of two different doses of the vac cine and will be monitored for the occurrence of any adverse reactions to it. In addition, we will determine whether the administration of t he vaccine induces and/or enhances tumor-specific host responses at th e immunological and/or clinical level.