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Long-term outcomes in patients with metastatic melanoma vaccinated with melanoma peptide-pulsed CD34+ progenitor-derived dendritic cells

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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.

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Acknowledgements

We thank our patients for volunteering to participate in our study. We are grateful to BiJue Chang, Doris Wood, and Susan Hicks for excellent help with patient accrual, follow-up, and regulatory issues. We thank Nicolas Taquet, Jennifer Finholt-Perry, and Leena John at BIIR GMP Lab for excellent work and commitment; John Kohl, Sebastien Coquery, and Elizabeth T. Kraus for processing and analysis of blood samples; Joseph Krasovsky for excellent technical assistance with immunologic monitoring; Cindy Samuelsen for continuous help. We thank Dr. Michael Ramsay for continuous support. We thank Dr. Jeff Weber for discussion and review of the manuscript. Supported by grants from Baylor Health Care Systems Foundation, Falk Foundation, Cancer Research Institute (JWF), Damon Runyon Cancer Research Fund, and Irene Diamond Foundation (MVD), the National Institutes of Health (CA78846 to JB, CA106802 to MVD, PO-1 CA84512 to RS), ARC (SP). JB is the recipient of the Caruth Chair for Transplantation Immunology Research. AKP is the recipient of the Michael A. Ramsay Chair for Cancer Immunology Research.

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Authors and Affiliations

  1. Baylor Institute for Immunology Research, 3434 Live Oak, Dallas, TX, 75204, USA

    Joseph W. Fay, A. Karolina Palucka, Sophie Paczesny, Susan Burkeholder, Hideki Ueno & Jacques Banchereau

  2. The Rockefeller University, New York, NY, USA

    Madhav Dhodapkar

  3. Hematology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Madhav Dhodapkar

  4. Department of Statistics, Baylor University, Waco, TX, USA

    Dennis A. Johnston

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  1. Joseph W. Fay
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  2. A. Karolina Palucka
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Correspondence to Joseph W. Fay.

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Joseph W. Fay and A. Karolina Palucka have equally contributed to this work

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Fay, J.W., Palucka, A.K., Paczesny, S. et al. Long-term outcomes in patients with metastatic melanoma vaccinated with melanoma peptide-pulsed CD34+ progenitor-derived dendritic cells. Cancer Immunol Immunother 55, 1209–1218 (2006). https://doi.org/10.1007/s00262-005-0106-6

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