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

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.

• Authors: W Joost Lesterhuis, I Jolanda M de Vries, Gerty Schreibelt, Annechien J A Lambeck, Erik H J G Aarntzen, Joannes F M Jacobs, Nicole M Scharenborg, Mandy W M M van de Rakt, Annemiek J de Boer, Sandra Croockewit, Michelle M van Rossum, Roel Mus, Wim J G Oyen, Otto C Boerman, Sophie Lucas, Gosse J Adema, Cornelis J A Punt, Carl G Figdor
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 17 Issue 17 Pg. 5725-35 (Sep 01 2011) ISSN: 1557-3265 [Electronic] United States
• PMID: 21771874 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2011 AACR.

Chemical References

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

Topics

• Adult
• Aged
• Antigens, Neoplasm (immunology)
• B-Lymphocytes (immunology)
• Cancer Vaccines (administration & dosage, immunology, 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, immunology)
• Lymph Nodes (immunology, pathology)
• Male
• Melanoma (immunology, therapy)
• Middle Aged
• Neoplasm Recurrence, Local
• T-Lymphocytes (immunology)
• Treatment Outcome