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

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Publication year
2011Source
Clinical Cancer Research, 17, 17, (2011), pp. 5725-35ISSN
Publication type
Article / Letter to editor

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Organization
Medical Oncology
Tumorimmunology
Paediatrics - OUD tm 2017
Laboratory of Medical Immunology
Haematology
Dermatology
Radiology
Nuclear Medicine
Journal title
Clinical Cancer Research
Volume
vol. 17
Issue
iss. 17
Page start
p. 5725
Page end
p. 35
Subject
N4i 1: Pathogenesis and modulation of inflammation; N4i 2: Invasive mycoses and compromised host ONCOL 3: Translational research; N4i 4: Auto-immunity, transplantation and immunotherapy NCMLS 2: Immune Regulation; ONCOL 2: Age-related aspects of cancer NCMLS 2: Immune Regulation; ONCOL 3: Translational research; ONCOL 3: Translational research NCMLS 2: Immune Regulation; ONCOL 5: Aetiology, screening and detectionAbstract
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 x 10 to 17 x 10 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 IFNgamma 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.
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- Academic publications [227864]
- Electronic publications [107337]
- Faculty of Medical Sciences [86218]
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