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

Tomoharu Miyashita, Furhawn A. Shah, Guy Marti, Jiaai Wang, Todd Armstrong, Pramod Bonde, Michael K. Gibson, Kiyoshi Yoshimura, Elizabeth A. Montgomery, Mark D. Duncan, Elizabeth M. Jaffee, John W. Harmon

Research output: Contribution to journalArticle

Abstract

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. 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. 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. 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.

Original languageEnglish (US)
Pages (from-to)2-9
Number of pages8
JournalJournal of Gastrointestinal Surgery
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2008

Keywords

  • Barrett's esophagus
  • Esophageal cancer
  • GM-CSF
  • Vaccine

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

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