title: Dendritic cell vaccination induces tumor epitope-specific Th1 immune response in medullary thyroid carcinoma.
abstract: The existence of inherited aggressive forms of medullary thyroid carcinoma (MTC) and their resistance to classical therapies make it a prime candidate for adoptive immunotherapy. Highly potent antigen-presenting cells, namely dendritic cells (DCs), may serve as an interesting tool for anticancer vaccination. Here we report on the IN VITRO findings of a vaccination trial in five MTC patients, who were treated with a new DC generation protocol consisting of granulocyte-macrophage colony-stimulating factor and interferon-alpha (IFN-DCs). These cells were pulsed with tumor-specific calcitonin and administered twice. In two patients who responded to therapy we found a large increase (in mean 2.9+/-1.9%) of antigen-specific IFN-gamma-secreting CD4+ cells as well as an increase of granzyme B positive CD8+ cells (mean 2.2+/-0.2%) in the peripheral blood. In parallel, a decrease of CD4+/CD25+/FoxP3+ regulatory T cells was seen. Importantly, IN VITRO stimulation of PBMC with 10 different 15mer calcitonin peptides resulted in the identification of two HLA class II epitope regions within the central part of full-length calcitonin. These data were in accordance with the results drawn from the computer-based algorithm epitope prediction software SYFPEITHI. Measurement of different pro- and anti-angiogenic factors did not allow for a distinct outcome of prediction of the treated patients. In summary, we have demonstrated that immunization with IFN-DCs leads to a tumor epitope-specific immune response in MTC patients and may, therefore, represent a promising tool for future vaccination trials.
authors.affiliation: Department of Endocrinology, Diabetes, and Rheumatology, University Hospital Duesseldorf, Duesseldorf, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Papewalis
authors.forename: M
authors.initials: M
authors.lastname: Wuttke
authors.forename: B
authors.initials: B
authors.lastname: Jacobs
authors.forename: J
authors.initials: J
authors.lastname: Domberg
authors.forename: H
authors.initials: H
authors.lastname: Willenberg
authors.forename: T
authors.initials: T
authors.lastname: Baehring
authors.forename: K
authors.initials: K
authors.lastname: Cupisti
authors.forename: A
authors.initials: A
authors.lastname: Raffel
authors.forename: L
authors.initials: L
authors.lastname: Chao
authors.forename: R
authors.initials: R
authors.lastname: Fenk
authors.forename: J
authors.initials: J
authors.lastname: Seissler
authors.forename: W A
authors.initials: WA
authors.lastname: Scherbaum
authors.forename: M
authors.initials: M
authors.lastname: Schott
mesh_terms: D000595:Amino Acid Sequence; D043925:Angiogenesis Inducing Agents / Q000097:blood / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology*; D002116:Calcitonin / Q000138:chemical synthesis / Q000276:immunology / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000138:chemical synthesis / Q000276:immunology / Q000627:therapeutic use*; D018276:Carcinoma, Medullary / Q000276:immunology* / Q000628:therapy; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D018604:Epitope Mapping; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D016898:Interferon-alpha / Q000276:immunology; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D013964:Thyroid Neoplasms / Q000276:immunology* / Q000628:therapy; D022223:Vaccines, Subunit / Q000138:chemical synthesis / Q000276:immunology / Q000627:therapeutic use
chemical_list: D043925:Angiogenesis Inducing Agents; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016898:Interferon-alpha; D022223:Vaccines, Subunit; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002116:Calcitonin