Dendritic cell immunotherapy induces antitumour response in parathyroid carcinoma and neuroendocrine pancreas carcinoma

Parathyroid carcinomas and neuroendocrine carcinomas of the pancreas are ra re malignancies in humans. Because of their low radio- and chemosensibility , they fail to respond to conventional therapy. We therefore tested a dendr itic cell immunotherapy in an attempt to control the tumour growth in two p atients. Studies on mice and humans have demonstrated the potent capacity o f dendritic cells to induce specific antitumour immunity. Mature dendritic cells were generated from peripheral blood monocytes in the presence of gra nulocyte/ macrophage colony-stimulating factor, interleukin 4 and tumour ne crosis factor alpha. Dendritic cells were either loaded with parathyroid ho rmone (PTH) or with (pancreas) tumour-derived lysate (TL), respectively, an d were delivered by subcutaneous injections. All immunizations were well to lerated with no side effects, and were administered on an outpatient basis. After repeated vaccinations, specific in vivo immune response was demonstr ated by positive delayed-type hypersensitivity (DTH) toward PTH or TL, demo nstrating the efficient generation of antigen-specific memory T-cells. DTH reactivity was accompanied by a significant decrease of tumour markers in b oth patients. This approach might be generally applicable to other advanced , radio- and chemotherapy-resistant endocrine malignancies.