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


CONCLUSIONS
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.
Morse
Michael A
MA
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Nair
Smita K
SK
Boczkowski
David
D
Tyler
Douglas
D
Hurwitz
Herbert I
HI
Proia
Alan
A
Clay
Timothy M
TM
Schlom
Jeffrey
J
Gilboa
Eli
E
Lyerly
H Kim
HK
D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000276:immunology / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy; D000231:Adenocarcinoma, Papillary / Q000188:drug therapy / Q000276:immunology / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000737:chemistry / Q000637:transplantation*; D018572:Disease-Free Survival; D005240:Feasibility Studies; D015789:HLA-A2 Antigen / Q000032:analysis; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007167:Immunotherapy; D020360:Neoadjuvant Therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D016577:Pancreaticoduodenectomy; D011184:Postoperative Period; D012333:RNA, Messenger / Q000008:administration & dosage* / Q000235:genetics; D018714:Radiotherapy, Adjuvant; D012449:Safety
D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen; D015789:HLA-A2 Antigen; D012333:RNA, Messenger