The Journal of Experimental Medicine
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Published online 1 June 2004 doi:10.1084/jem.20032118
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 11, 1503-1511
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Expansion of Melanoma-specific Cytolytic CD8+ T Cell Precursors in Patients with Metastatic Melanoma Vaccinated with CD34+ Progenitor-derived Dendritic Cells

Sophie Paczesny1, Jacques Banchereau1, Knut M. Wittkowski3, Giovanna Saracino2, Joseph Fay1, and A. Karolina Palucka1

1 Baylor Institute for Immunology Research and 2 Baylor University Medical Center, Dallas, TX 75204
3 General Clinical Research Center, The Rockefeller University, New York, NY 10021

Address correspondence to A. Karolina Palucka, Baylor Institute for Immunology Research, 3434 Live Oak, Dallas, TX 75204; Phone: (214) 820-7450; Fax: (214) 820-4813; email: karolinp{at}baylorhealth.edu; or Jacques Banchereau, Baylor Institute for Immunology Research, 3434 Live Oak, Dallas, TX 75204; Phone: (214) 820-7450; Fax: (214) 820-4813; email: jacquesb{at}baylorhealth.edu

Cancer vaccines aim at inducing (a) tumor-specific effector T cells able to reduce/eliminate the tumor mass, and (b) long-lasting tumor-specific memory T cells able to control tumor relapse. We have shown earlier, in 18 human histocompatibility leukocyte antigen (HLA)-A*0201 patients with metastatic melanoma, that vaccination with peptide-loaded CD34–dendritic cells (DCs) leads to expansion of melanoma-specific interferon {gamma}–producing CD8+ T cells in the blood. Here, we show in 9 out of 12 analyzed patients the expansion of cytolytic CD8+ T cell precursors specific for melanoma differentiation antigens. These precursors yield, upon single restimulation with melanoma peptide–pulsed DCs, cytotoxic T lymphocytes (CTLs) able to kill melanoma cells. Melanoma-specific CTLs can be grown in vitro and can be detected in three assays: (a) melanoma tetramer binding, (b) killing of melanoma peptide–pulsed T2 cells, and (c) killing of HLA-A*0201 melanoma cells. The cytolytic activity of expanded CTLs correlates with the frequency of melanoma tetramer binding CD8+ T cells. Thus, CD34-DC vaccines can expand melanoma-specific CTL precursors that can kill melanoma antigen–expressing targets. These results justify the design of larger follow-up studies to assess the immunological and clinical response to peptide-pulsed CD34-DC vaccines.

Key Words: tumor immunology • immunotherapy • cancer • vaccine • immunomonitoring

The online version of this article contains supplemental material.

Abbreviations used in this paper: CM, culture medium; CT, computed tomography; Flu-MP, flu-matrix peptide.


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