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Endokrine, neuroendokrine Tumoren

Schott M et al.: Dendritic cell immunotherapy in a neuroendocrine pancreas carcinoma. Clin Endocrinol (Oxf). 2001 Aug;55(2):271-7.


OBJECTIVE: Metastatic neuroendocrine carcinomas of the pancreas frequently fail to respond to conventional therapies, including radiation and chemotherapy. We therefore tested a dendritic cell-based immunotherapy in an attempt to eradicate residual tumour masses in a patient suffering from a metastatic insulin-producing pancreatic carcinoma.

DESIGN: Autologous dendritic cells (DCs) were generated from peripheral blood monocytes in the presence of granulocyte/macrophage colony-stimulating factor, interleukin-4 and tumour necrosis factor alpha. DCs were loaded with tumour-derived lysate (TL), and were delivered by subcutaneous injections in 4-week intervals.

RESULTS: Three weeks after first treatment, the patient developed a strong delayed-type hypersensitivity (DTH) skin reaction with an erythema and induration after the challenge with TL-pulsed DCs, which indicates the efficient generation of antigen-specific memory T-cells. Immunohistochemical analysis of skin biopsy demonstrated a strong perivascular and epidermal infiltration by T-helper (CD4 positive) and cytotoxic T cells (CD8 positive). Stimulation with TL revealed a dose-dependent T-cell proliferation with a stimulation index of 1.1-5.7 compared to 1.1-1.4 before vaccination (P < 0.01). Most strikingly, DC-based vaccination was accompanied by a steady decrease of the tumour marker chromogranin A from 2.93 umol/l initially to below the detection limit of 0.15 umol/l within 9 months of therapy. The ultrasound examination revealed a tumour regression of the metastasis in the right lobe of the liver.

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