Phase II Trial of Dendritic Cells Loaded with Antigens from Self-Renewing, Proliferating Autologous Tumor Cells as Patient-Specific Antitumor Vaccines in Patients with Metastatic Melanoma: Final Report

Between January 2001 and September 2007, we treated 54 metastatic melanoma patients with patient-specific tumor cell vaccines consisting of dendritic cells (DCS), derived from their peripheral blood cells that were cultured in interleukin (IL)-4 and granulocyte macrophage colony-stimulating factor (GM-CSF), which had phagocytosed irradiated autologous tumor cells from a continuously proliferating, self-renewing, autologus tumor cell (TC) culture. The loaded DCs were injected subcutaneously in 500 mu g of GM-CSF weekly x three, and then monthly for 5 months, for a total of up to 8 injections. The 34 men and 20 women had a median age of 50.5 years; 32 had M1c (visceral metastases and/or elevated lactate dehydrogenase) as their most advanced disease stage. Overall, 83% had received other systemic therapies, including interferon-alpha (n = 20), biochemotherapy (n = 19), GM-CSF (n = 19), chemotherapy (n = 16), IL-2 (n = 13), and other investigational vaccines (n = 7). Patients received an average of 7.4 vaccinations. Treatment was well-tolerated, with most patients experiencing only mild local pruritus and/or erythema. A positive delayed-type hypersensitivity reaction to purified autologous tumor cells was observed at baseline in only 1 of 54 patients, compared to 12 of 54 following vaccination (p = 0.001). The projected 5-year survival rate is an impressive 54% at a median follow-up of 4.5 years (range, 2.4-7.4) for the 30 surviving patients. This survival was superior to that observed following vaccination with irradiated TC in 48 melanoma patients in a previous trial (64 versus 31 months, p = 0.016). This patient-specific vaccine warrants further investigation, based on its safety and encouraging survival rates. (Clinical Trial Number: NCI-V01-1646).