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

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.