Abstract
2525 Background: Culture of CD34+ blood cells with GM-CSF, Flt-3 ligand and TNF yield distinct dendritic cell (DC) subtypes including Langerhans and interstitial DCs. Such composite DC vaccine was loaded with melanoma peptides (MART-1, tyrosinase, MAGE-3, gp100) and control antigens flu-matrix and KLH, and administered subcutaneously to patients with metastatic melanoma in a Phase I trial. Methods: HLA-A0201+patients received 4 DC vaccinations every 2 weeks followed by additional 4 monthly DC vaccinations. All DCs were pulsed with KLH, 20% of cells were pulsed with flu-matrix peptide and 80% with melanoma peptides. IFN-gamma ELISPOT and tetramer staining were used to measure specific CD8+ T cells. Spearman correlation was used with non-transformed data. Patient survival was calculated using Kaplan-Meier estimation based on log-rank analysis of difference. Results: There were 18 patients: 10 male with median age (range) was 53 (40–73) years. 6 patients had progressive melanoma after 4 vaccines and were removed from study. 12 patients received 5–8 consolidation DC vaccinations. There were no significant adverse events. The median (range) overall survival was 20 (2–69) months. At present there are 5 patients (27.7%, [95% c.i. 19.3–39.6]) who are alive at 55+, 61+, 61+, 61+ and 69+ months after their last vaccine. Production of IFN-gamma determined by ELISPOT to 3–4 melanoma antigens after 4 DC vaccinations correlated with overall survival (p=0.0065). Peptide tetramers of CD8+ T-cells validated Mart-1 and flu ELISPOTS. 5/5 long-term survivors had immunity to greater than 3 melanoma antigens after 4 vaccinations and at least 2 antigens after their last vaccination. Conclusions: Vaccination of patients with metastatic melanoma with melanoma peptide- loaded DCs made from CD34+ progenitor cells resulted in a broad melanoma antigen-specific CD8+ T-cell immune response that correlated with survival in a significant number of patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Argos Therapeutics, ODC Therapy
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