Immune and Clinical Outcomes in Patients with Stage IV Melanoma Vaccinated with Peptide-Pulsed Dendritic Cells Derived From CD34+ Progenitors and Activated with Type I Interferon

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Abstract
Twenty-two HLA A*0201+ patients with stage IV melanoma were enrolled in a phase 1 safety and feasibility trial using a composite dendritic cell (DC) vaccine generated by culturing CD34+ hematopoietic progenitors and activated with IFN-α. The DC vaccine was loaded with peptides derived from four melanoma tissue differentiation antigens (MART-1, tyrosinase, MAGE-3, and gp100) and influenza matrix peptide (Flu-MP). Twenty patients were evaluable, 14 of whom received vaccination with peptide-pulsed DCs without keyhole limpet hemocyanin (KLH) and 6 of whom received vaccination with KLH-loaded DCs. Patients were vaccinated until disease progression or until they had received eight vaccinations. None of the analyzed patients showed the expansion of melanoma-peptide-specific circulating effector memory T cells that secrete IFN-γ in direct ELISPOT. Melanoma-peptide-specific recall memory CD8+ T cells able to secrete IFN-γ and to proliferate could be detected in six of the seven analyzed patients. There were no objective clinical responses. The estimated median overall survival was 12 months (range 2-38), and the median event-free survival was 4 months (range 1-12). There was no statistically significant survival advantage in patients who received KLH-loaded vaccines. As of March 2005, four patients remained alive, 26+, 28+, 28+, and 36+ months. Three of them had received KLH-loaded vaccines and all of them had had additional therapy. Overall, these results suggest that IFN-α-activated CD34-DCs are safe but elicit only limited immune responses, underscoring the need to test different DC maturation factors.