Induction of strong and persistent MelanA/MART-1-specific immune responses by adjuvant dendritic cell-based vaccination of stage II melanoma patients

Authors

  • Andrea Tuettenberg,

    1. Department of Dermatology, Johannes Gutenberg-University, Langenbeckstraße 1, D-55101 Mainz, Germany
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    • The first 2 authors contributed equally to this work.

  • Christian Becker,

    Corresponding author
    1. Department of Dermatology, Johannes Gutenberg-University, Langenbeckstraße 1, D-55101 Mainz, Germany
    • Department of Dermatology, Johannes Gutenberg-University, Langenbeckstraße 1, D-55101 Mainz, Germany
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    • The first 2 authors contributed equally to this work.

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  • Eva Huter,

    1. Department of Dermatology, Johannes Gutenberg-University, Langenbeckstraße 1, D-55101 Mainz, Germany
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  • Jürgen Knop,

    1. Department of Dermatology, Johannes Gutenberg-University, Langenbeckstraße 1, D-55101 Mainz, Germany
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  • Alexander H. Enk,

    1. Department of Dermatology, Johannes Gutenberg-University, Langenbeckstraße 1, D-55101 Mainz, Germany
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  • Helmut Jonuleit

    1. Department of Dermatology, Johannes Gutenberg-University, Langenbeckstraße 1, D-55101 Mainz, Germany
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Abstract

A significant percentage of stage II melanoma patients (tumor thickness >1 mm) remain at risk of tumor recurrence after primary tumor excision. In this study, we used tumor antigen-pulsed dendritic cells as an adjuvant for immunization of these “high-risk” melanoma patients after resection of the primary tumor. A total of 13 patients were included and vaccinated 6 times every 14 days with autologous dendritic cells pulsed with a MelanA/MART-1 peptide in combination with a recall antigen. Antigen-specific immune responses were monitored before, during and up to 1 year after the last vaccination. The majority of patients exhibited increased recall antigen-specific CD4+ T cell responses upon vaccination. MelanA/MART-1-specific CD8+ T cells were expanded in 9/13 patients resulting in increased frequencies of memory cells in these patients. CD8+ T cells acquired the capacity to secrete IFN-γ, to proliferate in culture in response to the tumor antigen used for vaccination and postvaccine samples contained MelanA/MART-1-specific T cells that recognized also the natural MelanA/MART-1-antigen expressed by tumor cells. Moreover, vaccination induced a long-lived tumor antigen-specific DTH-reactivity in the majority of the patients, detectable even 12 months after the last immunization. These data demonstrate for the first time that vaccination with tumor antigen-pulsed dendritic cells in a clinically adjuvant setting induces strong and persistent antigen-specific T-cell responses in tumor-free stage II melanoma patients, suggesting that tumor protective T cell immunity can be achieved. © 2005 Wiley-Liss, Inc.

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