Expansion of melanoma-specific cytolytic CD8+ T cell precursors in patients with metastatic melanoma vaccinated with CD34+ progenitor-derived dendritic cells

Sophie Paczesny, Jacques Banchereau, Knut M. Wittkowski, Giovanna Saracino, Joseph Fay, A. Karolina Palucka

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

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 γ-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.

Original languageEnglish (US)
Pages (from-to)1503-1511
Number of pages9
JournalJournal of Experimental Medicine
Volume199
Issue number11
DOIs
StatePublished - Jun 7 2004
Externally publishedYes

Fingerprint

T-Lymphoid Precursor Cells
Dendritic Cells
Melanoma
Cytotoxic T-Lymphocytes
Melanoma-Specific Antigens
T-Lymphocytes
Peptides
Histocompatibility Antigens
HLA Antigens
Neoplasms
Vaccines
Cancer Vaccines
Differentiation Antigens
Interferons
Vaccination

Keywords

  • Cancer
  • Immunomonitoring
  • Immunotherapy
  • Tumor immunology
  • Vaccine

ASJC Scopus subject areas

  • Immunology

Cite this

Expansion of melanoma-specific cytolytic CD8+ T cell precursors in patients with metastatic melanoma vaccinated with CD34+ progenitor-derived dendritic cells. / Paczesny, Sophie; Banchereau, Jacques; Wittkowski, Knut M.; Saracino, Giovanna; Fay, Joseph; Palucka, A. Karolina.

In: Journal of Experimental Medicine, Vol. 199, No. 11, 07.06.2004, p. 1503-1511.

Research output: Contribution to journalArticle

Paczesny, Sophie ; Banchereau, Jacques ; Wittkowski, Knut M. ; Saracino, Giovanna ; Fay, Joseph ; Palucka, A. Karolina. / Expansion of melanoma-specific cytolytic CD8+ T cell precursors in patients with metastatic melanoma vaccinated with CD34+ progenitor-derived dendritic cells. In: Journal of Experimental Medicine. 2004 ; Vol. 199, No. 11. pp. 1503-1511.
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