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Immunotherapy for Medullary Thyroid Carcinoma by Dendritic Cell Vaccination

Department of Endocrinology (M.S., J.F.) and German Diabetes Research Institute (J.S., M.L., V.F., W.A.S.), Heinrich-Heine-University Duesseldorf, D-40225 Duesseldorf, Germany

Address all correspondence and requests for reprints to: Matthias Schott, M.D., Department of Endocrinology, Heinrich-Heine-University Duesseldorf, Moorenstr. 5, D-40225 Duesseldorf, Germany. E-mail: schottmt{at}uni-duesseldorf.de

Abstract

Recent studies suggest that immunization with autologeous dendritic cells (DCs) pulsed with tumor antigen result in protective immunity and rejection of established tumors in various human malignancies. The objective of this study was to develop a DC vaccination therapy in patients with metastasized medullary thyroid carcinoma (MTC). Mature DCs were generated from peripheral blood monocytes in the presence of granulocyte macrophage colony-stimulating factor, IL-4, and TNF. After loading with calcitonin and carcinoembryonic antigen (CEA) peptide, 2–5 x 10⁶ DCs were repeatedly delivered by sc injections.

During follow-up (mean, 13.1 months) all patients developed a strong delayed-type hypersensitivity skin reaction caused by perivascular and epidermal infiltration with CD4+ memory T cells and CD8+ cytotoxic T cells. Clinical responses with a decrease of serum calcitonin and CEA were initially documented in three of seven patients. One of these patients had a complete regression of detectable liver metastases and a significant reduction of pulmonary lesions. T-cell response in this patient revealed a calcitonin- and CEA-specific immunreactivity.

Our data indicate that vaccination with calcitonin and/or CEA peptide-pulsed DC results in the induction of a cellular, antigen-specific immune response in patients with MTC, leading to clinical response in some patients. Our approach may represent the basis for the development of new therapeutic strategies not only in MTC but also in other endocrine malignancies.

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