Calcitonin-specific antitumor immunity in medullary thyroid carcinoma following dendritic cell vaccination.
In this study, we investigated the immune response following immunotherapy with calcitonin-pulsed dendritic cells (DC) in 7 patients with metastasized medullary thyroid carcinoma. After immunization with 1-5 x 10(6) autologous DC, significant calcitonin-specific T cell proliferation was detectable in 3 patients. Measurement of cytokine release from T lymphocytes demonstrated high post-treatment interferon-gamma (IFN-gamma) secretion after stimulation with calcitonin in 5 patients, one of whom experienced significant tumor regression. In contrast, antigen-specific interleukin-4 (IL-4) production was only slightly increased in 4 patients. All 7 patients developed a strong delayed-type hypersensitivity (DTH) skin reaction, which was confirmed to be mediated by infiltrating CD4+ T-helper cells and CD8+ cytotoxic T cells in all 3 patients who underwent skin biopsy. This is the first study to show that a polypeptide hormone can be used to develop a DC vaccination strategy for the immunotherapy of highly malignant endocrine cancers.
Schott
Matthias
M
Department of Endocrinology, Heinrich Heine University Dusseldorf, Moorenstrasse 5, 40225 Dusseldorf, Germany. schottmt@uni-duesseldorf.de
Feldkamp
Joachim
J
Klucken
Melanie
M
Kobbe
Guido
G
Scherbaum
Werner A
WA
Seissler
Jochen
J
D000328:Adult; D002116:Calcitonin / Q000276:immunology*; D018276:Carcinoma, Medullary / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007150:Immunohistochemistry; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D013964:Thyroid Neoplasms / Q000276:immunology / Q000628:therapy*; D014611:Vaccination
D016207:Cytokines; D002116:Calcitonin