Vaccine impedes the development of reflux-induced esophageal cancer in a surgical rat model: efficacy of the vaccine in a Pre-Barrett's esophagus setting.
OBJECTIVE
We developed a granulocyte-macrophage-colony-stimulating factor (GM-CSF) tumor vaccine for esophageal cancer. We evaluated the effectiveness of the vaccine as a prevention option in a surgical reflux rat model of esophageal cancer.


METHODS
A surgical model involving a jejuno-esophagostomy was used to create Barrett's esophagus and esophageal cancer in rats. No carcinogen exposure was utilized. Cell lines derived from these tumors were stably passaged in vitro. GM-CSF-secreting tumor cells were generated using stable transfection. All rats underwent a total gastrectomy, followed by a jejuno-esophagostomy. The surgery promoted the reflux of duodenal contents into the esophagus. All animals were administered either a GM-CSF secreting whole cell vaccine or a phosphate-buffered saline (PBS) placebo injection 4, 6, 14, and 16 weeks post-surgery.


RESULTS
While 15 of 16 animals in the non-vaccinated placebo group developed esophageal cancer, 94% (15 of 16), animals in the vaccine group had an incidence of cancer of 25% (4 of 16) (p<0.05). Barrett's esophagus was seen in 100% (16 of 16) of the controls and 83% (13 of 16) of the vaccinated animals.


CONCLUSIONS
A GM-CSF-secreting whole cell tumor vaccine impeded esophageal tumor growth, but not the development of Barrett's esophagus, in a clinically relevant surgical reflux model.
Miyashita
Tomoharu
T
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Shah
Furhawn A
FA
Marti
Guy
G
Wang
Jiaai
J
Armstrong
Todd
T
Bonde
Pramod
P
Gibson
Michael K
MK
Yoshimura
Kiyoshi
K
Montgomery
Elizabeth A
EA
Duncan
Mark D
MD
Jaffee
Elizabeth M
EM
Harmon
John W
JW
D000230:Adenocarcinoma / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D001471:Barrett Esophagus / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004942:Esophagitis, Peptic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004946:Esophagostomy / Q000009:adverse effects*; D005500:Follow-Up Studies; D005743:Gastrectomy / Q000009:adverse effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D007081:Ileostomy / Q000009:adverse effects*; D009374:Neoplasms, Experimental; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor