T cell responses in melanoma patients after vaccination with tumor-mRNA transfected dendritic cells

Cancer Immunol Immunother. 2007 May;56(5):659-75. doi: 10.1007/s00262-006-0222-y. Epub 2006 Sep 1.


We have developed an individualized melanoma vaccine based on autologous dendritic cells (DCs) transfected with autologous tumor-mRNA. The vaccine targets the unique spectrum of tumor antigens in each patient and may recruit multiple T cell clones. In a recent phase I/II trial, we demonstrated T cell responses against vaccine antigens in 9/19 patients evaluable by T cell assays. Here, we report a follow-up study that was conducted to characterize interesting T cell responses and to investigate the effects of long-term booster vaccination. Two patients were selected for continued vaccine therapy. The clinical follow-up suggested a favorable clinical development in both patients. The immunological data (T cell proliferation/IFNgamma ELISPOT/Bioplex cytokine assays) indicated sustained T cell responses and suggested an enhancing effect of booster vaccinations. Both CD4(+) and CD8(+) T cell responses were demonstrated. From post-vaccination samples, we generated 39 T cell clones that responded specifically to stimulation by mRNA-transfected DCs and 12 clones that responded to mock-transfected DCs. These data clearly indicate a two-component vaccine response, against transfected and non-transfected antigens. T cell receptor (TCR) clonotype mapping, performed on 11 tDC-specific clones, demonstrated that 10/11 clones had different TCRs. The results thus indicate a broad spectrum T cell response against antigens encoded by the transfected tumor-mRNA. We generally observed mixed Th1/Th2 cytokine profiles, even in T cell clones that were confirmed to be derived from a single cell. This finding suggests that cytokine patterns after cancer vaccination may be more complex than indicated by the classic Th1/Th2 dichotomy.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Female
  • Humans
  • Male
  • Melanoma / immunology
  • Melanoma / therapy*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / immunology
  • RNA, Neoplasm / therapeutic use*
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / immunology*
  • Transfection


  • Cancer Vaccines
  • Cytokines
  • RNA, Neoplasm
  • Receptors, Antigen, T-Cell