Abstract
Background:
Resected pancreatic cancer has a high risk of recurrence and mortality despite the the use of chemoradiotherapy. Because pancreatic cancers express tumor antigens such as carcinoembryonic antigen (CEA), it may be possible to immunize patients to induce tumor antigen-specific immune responses. We hypothesize that high-frequency tumor antigen-specific immune responses will reduce recurrence and increase survival. Autologous dendritic cells (DCs) loaded with tumor antigens are particularly potent at inducing tumor antigen-specific immune responses.
Methods:
Three patients with resected pancreatic adenocarcinoma following neoadjuvant chemoradiotherapy received autologous, monocyte-derived DCs loaded with the mRNA encoding CEA monthly for 6 mo.
Results:
It was feasible to generate an adequate number of DC from these patients and to cryopreserve them for repeated use. The DC demonstrated the typical immature phenotype. The immunizations were well-tolerated without evidence of adverse events. All three developed injection site reactivity. All three are alive without evidence of disease at more than 2 1/2 yr from the original diagnosis.
Conclusion:
The postoperative period following neoadjuvant chemoradiotherapy and pancreaticoduodenectomy for pancreatic cancer is an ideal environment to test novel immune-based therapies. DC-based immunotherapy in this setting is safe and feasible and may lead to prolonged survival.
Publication types
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Evaluation Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenocarcinoma / drug therapy
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Adenocarcinoma / immunology
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Adenocarcinoma / radiotherapy
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Adenocarcinoma / surgery
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Adenocarcinoma / therapy*
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Adenocarcinoma, Mucinous / drug therapy
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Adenocarcinoma, Mucinous / immunology
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Adenocarcinoma, Mucinous / radiotherapy
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Adenocarcinoma, Mucinous / surgery
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Adenocarcinoma, Mucinous / therapy
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Adenocarcinoma, Papillary / drug therapy
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Adenocarcinoma, Papillary / immunology
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Adenocarcinoma, Papillary / radiotherapy
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Adenocarcinoma, Papillary / surgery
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Adenocarcinoma, Papillary / therapy
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Aged
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology*
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Carcinoembryonic Antigen / genetics
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Carcinoembryonic Antigen / immunology*
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Chemotherapy, Adjuvant*
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Combined Modality Therapy
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Dendritic Cells / chemistry
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Dendritic Cells / transplantation*
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Disease-Free Survival
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Feasibility Studies
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HLA-A2 Antigen / analysis
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Humans
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Hypersensitivity, Delayed / immunology
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Immunotherapy*
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Neoadjuvant Therapy*
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Pancreatic Neoplasms / drug therapy
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Pancreatic Neoplasms / immunology
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Pancreatic Neoplasms / radiotherapy
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Pancreatic Neoplasms / surgery
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Pancreatic Neoplasms / therapy*
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Pancreaticoduodenectomy*
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Postoperative Period
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RNA, Messenger / administration & dosage*
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RNA, Messenger / genetics
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Radiotherapy, Adjuvant*
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Safety
Substances
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Antigens, Neoplasm
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Carcinoembryonic Antigen
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HLA-A2 Antigen
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RNA, Messenger