Boosting vaccinations with peptide-pulsed CD34+ progenitor-derived dendritic cells can expand long-lived melanoma peptide-specific CD8+ T cells in patients with metastatic melanoma

J Immunother. 2005 Mar-Apr;28(2):158-68. doi: 10.1097/01.cji.0000154249.74383.17.

Abstract

The immunogenicity of dendritic cell (DC)-based vaccines has been shown in patients with advanced cancer, but it has not yet been established whether the elicited cancer-specific immunity is durable and whether it can be maintained by boosting vaccinations. The authors showed earlier, in 18 HLA-A*0201 metastatic melanoma patients, that four vaccinations over 6 weeks with peptide-loaded CD34-DCs (the induction phase) expand in the blood melanoma-specific CD8+ T cells, as documented by melanoma peptide-specific IFN-gamma ELISPOT and cytotoxic T-lymphocyte (CTL) activity against melanoma cell lines. The authors show here that the melanoma peptide-specific CD8+ T-cell immunity is short-lived, but it could be reactivated in 7 of 11 patients who received four boosting vaccinations with peptide-loaded CD34-DCs. Expansion of recall memory CD8+ T cells was confirmed by tetramer binding and CTL activity against melanoma peptide-pulsed T2 cells. In two patients boosted over 15 months, induced melanoma peptide-specific recall memory CD8+ T cells lasted at least 6 months. Thus, boosting vaccination with peptide-loaded CD34-DCs can expand long-lived tumor peptide-specific immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD34 / biosynthesis*
  • CD8-Positive T-Lymphocytes / cytology*
  • Cancer Vaccines*
  • Dendritic Cells / cytology*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / cytology
  • Melanoma / immunology
  • Melanoma / metabolism
  • Melanoma / therapy*
  • Neoplasm Metastasis
  • Peptides / chemistry
  • Time Factors

Substances

  • Antigens, CD34
  • Cancer Vaccines
  • Peptides
  • Interferon-gamma