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

J Gastrointest Surg. 2008 Jan;12(1):2-7; discussion 7-9. doi: 10.1007/s11605-007-0337-2. Epub 2007 Oct 24.

Abstract

Background & aims: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / etiology
  • Adenocarcinoma / pathology
  • Adenocarcinoma / prevention & control
  • Animals
  • Barrett Esophagus / complications
  • Barrett Esophagus / drug therapy*
  • Barrett Esophagus / pathology
  • Cancer Vaccines / therapeutic use*
  • Carcinoma, Squamous Cell / etiology
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / prevention & control
  • Cell Line, Tumor
  • Esophageal Neoplasms / etiology
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / prevention & control*
  • Esophagitis, Peptic / complications
  • Esophagitis, Peptic / drug therapy*
  • Esophagitis, Peptic / pathology
  • Esophagostomy / adverse effects*
  • Follow-Up Studies
  • Gastrectomy / adverse effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Ileostomy / adverse effects*
  • Neoplasms, Experimental
  • Rats
  • Rats, Sprague-Dawley
  • Treatment Outcome

Substances

  • Cancer Vaccines
  • Granulocyte-Macrophage Colony-Stimulating Factor