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

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

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  • 1Department of Medical Oncology,Nijmegen Centre for Molecular Life Sciences, and Laboratory of Medical Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Abstract

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.

©2011 AACR.

PMID:
21771874
[PubMed - indexed for MEDLINE]
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