Induction of strong and persistent MelanA/MART-1-specific immune responses by adjuvant dendritic cell-based vaccination of stage II melanoma patients
✍ Scribed by Andrea Tuettenberg; Christian Becker; Eva Huter; Jürgen Knop; Alexander H. Enk; Helmut Jonuleit
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- French
- Weight
- 607 KB
- Volume
- 118
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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.