Induction of cellular immunity in a parathyroid carcinoma treated with tumor lysate-pulsed dendritic cells

Background: Cytotoxic T-lymphocyte-mediated tumor immunity against major hi stocompatibility antigen class II-negative tumors requires help from CD4(+) T-cells, The major antigen presenting cells for CD4(+) cell activation are dendritic cells. Studies in mice and humans have demonstrated the potent c apacity of these cells to induce specific antitumor immunity. Objective: To control the growth of a metastasized parathyroid carcinoma, b y immunizing a patient with tumor lysate and parathyroid hormone-pulsed den dritic cells. Design and Methods: Mature dendritic cells were generated from peripheral b lood monocytes in the presence of granulocyte/macrophage colony-stimulating factor interleukin-4 and tumor necrosis factor alpha. Antigen-loaded dendr itic cells were delivered by subcutaneous and intralymphatical injections. After five cycles, we added keyhole limpet hemocyanin (KLHP) as a CD4(+) he lper antigen. Results: After 10 vaccinations, a specific cellular immune response to tumo r lysate was observed. In vitro T-cell proliferation assays revealed a dose -dependent stimulation index of 1.8-5.7 compared with 0.9-1.1 before vaccin ation. In vivo immune response was demonstrated by positive delayed-type hy persensitivity toward tumor lysate. Intradermal injection of tumor lysate r esulted in an erythema and induration, suggesting the efficient generation of tumor lysate-specific memory T-cells. Conclusions: These data indicate that dendritic cell vaccination can induce in vitro and in vivo responses in a highly malignant endocrine carcinoma. Regardless of the clinical outcome of our patient, this approach might be g enerally applicable to other advanced, radio- and chemotherapy-resistant en docrine malignancies, such as adrenal carcinomas and metastasized medullary and anaplastic thyroid carcinomas.