Route of administration modulates the induction of dendritic cell vaccine-induced antigen-specific T cells in advanced melanoma patients

Clin Cancer Res. 2011 Sep 1;17(17):5725-35. doi: 10.1158/1078-0432.CCR-11-1261. Epub 2011 Jul 19.


Purpose: It is unknown whether the route of administration influences dendritic cell (DC)-based immunotherapy. We compared the effect of intradermal versus intranodal administration of a DC vaccine on induction of immunologic responses in melanoma patients and examined whether concomitant administration of interleukin (IL)-2 increases the efficacy of the DC vaccine.

Experimental design: HLA-A2.1(+) melanoma patients scheduled for regional lymph node dissection were vaccinated four times biweekly via intradermal or intranodal injection with 12 × 10⁶ to 17 × 10⁶ mature DCs loaded with tyrosinase and gp100 peptides together with keyhole limpet hemocyanin (KLH). Half of the patients also received low-dose IL-2 (9 MIU daily for 7 days starting 3 days after each vaccination). KLH-specific B- and T-cell responses were monitored in blood. gp100- and tyrosinase-specific T-cell responses were monitored in blood by tetramer analysis and in biopsies from delayed-type hypersensitivity (DTH) skin tests by tetramer and functional analyses with (51)Cr release assays or IFNγ release, following coculture with peptide-pulsed T2 cells or gp100- or tyrosinase-expressing tumor cells.

Results: In 19 of 43 vaccinated patients, functional tumor antigen-specific T cells could be detected. Although significantly more DCs migrated to adjacent lymph nodes upon intranodal vaccination, this was also highly variable with a complete absence of migration in 7 of 24 intranodally vaccinated patients. Intradermal vaccinations proved superior in inducing functional tumor antigen-specific T cells. Coadministration of IL-2 did not further augment the antigen-specific T-cell response but did result in higher regulatory T-cell frequencies.

Conclusion: Intradermal vaccination resulted in superior antitumor T-cell induction when compared with intranodal vaccination. No advantage of additional IL-2 treatment could be shown.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / immunology
  • B-Lymphocytes / immunology
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use
  • Dendritic Cells / immunology*
  • Drug Administration Routes
  • Female
  • Forkhead Transcription Factors / biosynthesis
  • HLA-A2 Antigen / immunology
  • Hemocyanins / immunology
  • Humans
  • Immunotherapy
  • Injections, Intradermal
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / immunology
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Male
  • Melanoma / immunology*
  • Melanoma / therapy*
  • Middle Aged
  • Neoplasm Recurrence, Local
  • T-Lymphocytes / immunology
  • Treatment Outcome


  • Antigens, Neoplasm
  • Cancer Vaccines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • HLA-A2 Antigen
  • Interleukin-2
  • Hemocyanins
  • keyhole-limpet hemocyanin