Long-term outcomes in patients with metastatic melanoma vaccinated with melanoma peptide-pulsed CD34+ progenitor-derived dendritic cells |
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Authors: | Joseph W. Fay A. Karolina Palucka Sophie Paczesny Madhav Dhodapkar Dennis A. Johnston Susan Burkeholder Hideki Ueno Jacques Banchereau |
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Affiliation: | (1) Baylor Institute for Immunology Research, 3434 Live Oak, Dallas, TX 75204, USA;(2) The Rockefeller University, New York, NY, USA;(3) Hematology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA;(4) Department of Statistics, Baylor University, Waco, TX, USA |
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Abstract: | Between March 1999 and May 2000, 18 HLA-A*0201+ patients with metastatic melanoma were enrolled in a phase I trial using a dendritic cell (DC) vaccine generated by culturing CD34+ hematopoietic progenitors. This vaccine includes Langerhans cells. The DC vaccine was loaded with four melanoma peptides (MART-1/MelanA, tyrosinase, MAGE-3, and gp100), Influenza matrix peptide (Flu-MP), and keyhole limpet hemocyanin (KLH). Ten patients received eight vaccinations, one patient received six vaccinations, one patient received five vaccinations, and six patients received four vaccinations. Peptide-specific immunity was measured by IFN-γ production and tetramer staining in blood mononuclear cells. The estimated median overall survival was 20 months (range: 2–83), and the median event-free survival was 7 months (range: 2–83). As of August 2005, four patients are alive (three patients had M1a disease and one patient had M1c disease). Three of them have had no additional therapy since trial completion; two of them had solitary lymph node metastasis, and one patient had liver metastasis. Patients who survived longer were those who mounted melanoma peptide-specific immunity to at least two melanoma peptides. The present results therefore justify the design of larger follow-up studies to assess the immunological and clinical outcomes in patients with metastatic melanoma vaccinated with peptide-pulsed CD34-derived DCs.Joseph W. Fay and A. Karolina Palucka have equally contributed to this work |
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