Immunotherapy for medullary thyroid carcinoma by dendritic cell vaccination

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 peripher al blood monocytes in the presence of granulocyte macrophage colony-stimula ting factor, IL-4, and TNF alpha. After loading with calcitonin and carcino embryonic antigen (CEA) peptide, 2-5 x 10(6) DCs were repeatedly delivered by sc injections. During follow-up (mean, 13.1 months) all patients developed a strong delaye d-type hypersensitivity skin reaction caused by perivascuIar 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 docume nted in three of seven patients. One of these patients had a complete regre ssion of detectable liver metastases and a significant reduction of pulmona ry 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-pulse d DC results in the induction of a cellular, antigen-specific immune respon se in patients with MTC, leading to clinical response in some patients. Our approach may represent the basis for the development of new therapeutic st rategies not only in MTC but also in other endocrine malignancies.