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Dendritic cell immunotherapy in a neuroendocrine pancreas carcinoma
Author(s) -
Schott Matthias,
Feldkamp Joachim,
Lettmann Melanie,
Simon Dietmar,
Scherbaum Werner A.,
Seissler Jochen
Publication year - 2001
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.2001.01293.x
Subject(s) - immunotherapy , medicine , pancreas , neuroendocrine carcinoma , endocrinology , dendritic cell , carcinoma , cancer research , immune system , immunology , cancer
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 α. 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. CONCLUSIONS Our data indicate that vaccination with tumour lysate‐pulsed DCs induced a significant antitumour immune response in a neuroendocrine carcinoma of the pancreas. This approach represents an alternative strategy for the treatment of advanced neuroendocrine carcinomas that are resistant to conventional therapy.