Cancer Immunology, Immunotherapy

, Volume 60, Issue 2, pp 249–260

Wild-type and modified gp100 peptide-pulsed dendritic cell vaccination of advanced melanoma patients can lead to long-term clinical responses independent of the peptide used

  • W. Joost Lesterhuis
  • Gerty Schreibelt
  • Nicole M. Scharenborg
  • H. Mary-lène H. Brouwer
  • Marie-Jeanne P. Gerritsen
  • Sandra Croockewit
  • Pierre G. Coulie
  • Ruurd Torensma
  • Gosse J. Adema
  • Carl G. Figdor
  • I. Jolanda M. de Vries
  • Cornelis J. A. Punt
Original Article

DOI: 10.1007/s00262-010-0942-x

Cite this article as:
Lesterhuis, W.J., Schreibelt, G., Scharenborg, N.M. et al. Cancer Immunol Immunother (2011) 60: 249. doi:10.1007/s00262-010-0942-x

Abstract

Dendritic cell (DC)-based immunotherapy is explored worldwide in cancer patients. Several strategies have been employed to load DC with antigen, including peptide loading. To increase immunogenicity of peptides, major histocompatibility complex (MHC) class I binding affinity and stability of peptide–MHC complexes at the cell surface may be improved by modification of the amino acid sequence. In this study, we compared the capacity of DC loaded with wild-type versus modified gp100 peptides with higher binding affinities to induce an immune and clinical response in advanced melanoma patients. Metastatic HLA-A2.1+ melanoma patients were vaccinated intravenously (on average 25 × 106 DC) and intradermally (on average 11 × 106 DC) with mature DC loaded with keyhole limpet hemocyanin (KLH) together with tyrosinase peptide and either wild-type (15 patients) or modified (12 patients) gp100 peptides. All vaccinated patients showed a pronounced proliferative T cell or humoral response against KLH. Gp100-specific T cell responses were monitored in post-treatment delayed type hypersensitivity (DTH) skin biopsies by tetramer and functional analysis. Antigen-specific T cells were found in 2 of 15 patients vaccinated with wild-type gp100-loaded DC, versus 1 of 12 patients vaccinated with modified peptide-loaded DC. These three patients also had the best clinical response, with long-term (>8 years) complete responses in two patients, one in each group. We conclude that vaccination with peptide-loaded DC can result in long-term clinical responses in a minority of metastatic melanoma patients, and that the use of modified as compared to wild-type gp100 peptides for DC loading does not result in a relevant enhanced immune responses.

Keywords

Dendritic cells Immunotherapy Altered-peptide ligands Melanoma Monitoring 

Supplementary material

262_2010_942_MOESM1_ESM.pdf (17 kb)
Supplementary material 1 (PDF 16 kb)

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • W. Joost Lesterhuis
    • 1
  • Gerty Schreibelt
    • 2
  • Nicole M. Scharenborg
    • 2
  • H. Mary-lène H. Brouwer
    • 2
  • Marie-Jeanne P. Gerritsen
    • 3
  • Sandra Croockewit
    • 4
  • Pierre G. Coulie
    • 5
  • Ruurd Torensma
    • 2
  • Gosse J. Adema
    • 2
  • Carl G. Figdor
    • 2
  • I. Jolanda M. de Vries
    • 2
  • Cornelis J. A. Punt
    • 1
  1. 1.Department of Medical OncologyRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  2. 2.Department of Tumor ImmunologyNijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical CentreNijmegenThe Netherlands
  3. 3.Department of DermatologyRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  4. 4.Department of HematologyRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  5. 5.de Duve InstituteUniversité Catholique de LouvainBrusselsBelgium

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