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


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 alpha. 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.
Schott
M
M
Department of Endocrinology, Heinrich Heine University, Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany. schottmt@uni-duesseldorf.de
Feldkamp
J
J
Schattenberg
D
D
Krueger
T
T
Dotzenrath
C
C
Seissler
J
J
Scherbaum
W A
WA
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002277:Carcinoma / Q000276:immunology* / Q000628:therapy*; D003713:Dendritic Cells; D005260:Female; D005434:Flow Cytometry; D006433:Hemocyanins / Q000627:therapeutic use*; D006801:Humans; D007111:Immunity, Cellular; D008875:Middle Aged; D010282:Parathyroid Neoplasms / Q000276:immunology* / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016896:Treatment Outcome
D019496:Cancer Vaccines; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin