The feasibility and safety of immunotherapy with dendritic cells loaded with CEA mRNA following neoadjuvant chemoradiotherapy and resection of pancreatic cancer

Michael A. Morse, Smita K. Nair, David Boczkowski, Douglas Tyler, Herbert I. Hurwitz, Alan Proia, Timothy M. Clay, Jeffrey Schlom, Eli Gilboa, H. Kim Lyerly

Research output: Contribution to journalArticle

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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 21/2 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.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalInternational Journal of Gastrointestinal Cancer
Volume32
Issue number1
StatePublished - 2002
Externally publishedYes

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Carcinoembryonic Antigen
Chemoradiotherapy
Neoplasm Antigens
Pancreatic Neoplasms
Immunotherapy
Dendritic Cells
Safety
Messenger RNA
Recurrence
Pancreaticoduodenectomy
Survival
Postoperative Period
Monocytes
Immunization
Adenocarcinoma
Phenotype
Injections
Mortality

Keywords

  • CEA
  • Dendritic cells
  • Immunotherapy
  • mRNA
  • Pancreatic cancer

ASJC Scopus subject areas

  • Gastroenterology
  • Endocrinology
  • Oncology

Cite this

The feasibility and safety of immunotherapy with dendritic cells loaded with CEA mRNA following neoadjuvant chemoradiotherapy and resection of pancreatic cancer. / Morse, Michael A.; Nair, Smita K.; Boczkowski, David; Tyler, Douglas; Hurwitz, Herbert I.; Proia, Alan; Clay, Timothy M.; Schlom, Jeffrey; Gilboa, Eli; Lyerly, H. Kim.

In: International Journal of Gastrointestinal Cancer, Vol. 32, No. 1, 2002, p. 1-6.

Research output: Contribution to journalArticle

Morse, Michael A. ; Nair, Smita K. ; Boczkowski, David ; Tyler, Douglas ; Hurwitz, Herbert I. ; Proia, Alan ; Clay, Timothy M. ; Schlom, Jeffrey ; Gilboa, Eli ; Lyerly, H. Kim. / The feasibility and safety of immunotherapy with dendritic cells loaded with CEA mRNA following neoadjuvant chemoradiotherapy and resection of pancreatic cancer. In: International Journal of Gastrointestinal Cancer. 2002 ; Vol. 32, No. 1. pp. 1-6.
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AU - Morse, Michael A.

AU - Nair, Smita K.

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AU - Tyler, Douglas

AU - Hurwitz, Herbert I.

AU - Proia, Alan

AU - Clay, Timothy M.

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AU - Gilboa, Eli

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N2 - 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 21/2 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.

AB - 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 21/2 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.

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