Induction of strong and persistent MelanA/MART-1-specific immune responses by adjuvant dendritic cell-based vaccination of stage II melanoma patients.
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-gamma, 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.
Tuettenberg
Andrea
A
Department of Dermatology, Johannes Gutenberg-University, Langenbeckstrasse 1, D-55101 Mainz, Germany.
Becker
Christian
C
Huter
Eva
E
Knop
Jürgen
J
Enk
Alexander H
AH
Jonuleit
Helmut
H
D000276:Adjuvants, Immunologic; D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D009363:Neoplasm Proteins / Q000276:immunology*; D012878:Skin Neoplasms / Q000276:immunology* / Q000628:therapy*; D016896:Treatment Outcome; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins