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

Abstract

Background: Cytotoxic T-lymphocyte-mediated tumor immunity against major histocompatibility 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 capacity of these cells to induce specific antitumor immunity. Objective: To control the growth of a metastasized parathyroid carcinoma, by immunizing a patient with tumor lysate and parathyroid hormone-pulsed dendritic cells. Design and Methods: Mature dendritic cells were generated from peripheral blood monocytes in the presence of granulocyte/macrophage colony-stimulating factor, interleukin-4 and tumor necrosis factor α. Antigen-loaded dendritic cells were delivered by subcutaneous and intralymphatical injections. After five cycles, we added keyhole limpet hemocyanin (KLH) as a CD4+ helper antigen. Results: After 10 vaccinations, a specific cellular immune response to tumor 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 vaccination. In vivo immune response was demonstrated by positive delayed- type hypersensitivity toward tumor lysate. Intradermal injection of tumor lysate resulted 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 generally applicable to other advanced, radio- and chemotherapy-resistant endocrine malignancies, such as adrenal carcinomas and metastasized medullary and anaplastic thyroid carcinomas.