Calcitonin-specific antitumor immunity in medullary thyroid carcinoma following dendritic cell vaccination

Abstract.

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 1–5×10⁶ 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-γ (IFN-γ) 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.