Vaccination with a synthetic nonapeptide expressed in human tumors prevents colorectal cancer liver metastases in syngeneic rats

In previous studies, the antigen CSH‐275 (RTNKEASIC) was found expressed in tissue specimens from colorectal cancer but not in normal colonic mucosa. It was also naturally expressed in the DHD‐K12 experimental colorectal cancer in BDIX rats. In this study, we describe the effect of vaccination with the synthetic nonapeptide CSH‐275 in preventing tumor growth in a model closely mimicking the clinical situation of liver metastases, after surgical resection of primary colorectal cancer. A vaccination protocol using CSH‐275, conjugated with complete or incomplete Freund's adjuvant, was carried out to determine the effect in preventing the progression of liver metastases induced by DHD‐K12 cells injected in the splenic vein (preventive vaccine). An additional vaccination procedure was carried out to determine the effect on s.c. tumor growth (therapeutic vaccine). A significant improvement in survival along with the prevention of liver metastases formation and reduced growth of s.c. tumor were observed. CSH‐275 vaccination resulted in a significant increase in CTL activity against autologous DHD‐K12 cells in DHD‐K12 tumor‐bearing rats and the generation of a CTL response against DHD‐K12 cells in DHD‐K12 naive rats. Vaccination also induced massive infiltration of CD8+ cells in tumor. These results demonstrate that CSH‐275 is a new molecular target for colorectal cancer immunotherapy; it is also an excellent candidate for preclinical studies because it is naturally expressed on tumors in a fully competent syngeneic animal, which reproduces the clinical pattern of cancer progression. © 2004 Wiley‐Liss, Inc.