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Horm Metab Res 2008; 40(2): 108-116
DOI: 10.1055/s-2007-1022565
Original

© Georg Thieme Verlag KG Stuttgart · New York

Dendritic Cell Vaccination Induces Tumor Epitope-specific Th1 Immune Response in Medullary Thyroid Carcinoma

C. Papewalis 1 , M. Wuttke 1 , B. Jacobs 1 , J. Domberg 1 , H. Willenberg 1 , T. Baehring 1 , K. Cupisti 2 , A. Raffel 2 , L. Chao 1 , R. Fenk 3 , J. Seissler 4 , W. A. Scherbaum 1 , M. Schott 1
  • 1Department of Endocrinology, Diabetes, and Rheumatology, University Hospital Duesseldorf, Duesseldorf, Germany
  • 2Department of General, Visceral, and Pediatric Surgery, University Hospital Duesseldorf, Duesseldorf, Germany
  • 3Department of Hematology, Oncology, and Clinical Immunology, University Hospital Duesseldorf, Duesseldorf, Germany
  • 4Medical Clinic Innenstadt, Ludwig-Maximilians-University Munich, Munich, Germany
Further Information

Publication History

received 07.12.2007

accepted 21.12.2007

Publication Date:
19 February 2008 (online)

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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-α (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-γ-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.

Key words

dendritic cells - interferon-α - immunotherapy - medullary thyroid carcinoma - calcitonin - epitopes

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Correspondence

M. SchottMD 

Department of Endocrinology

Diabetes and Rheumatology

University Hospital Duesseldorf

Moorenstr.5

40225 Duesseldorf

Germany

Phone: +49/211/811 78 10

Fax: +49/211/811 78 60

Email: schottmt@uni-duesseldorf.de

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