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.
Sinibaldi Vallebona
Paola
P
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Rome, Italy.
Rasi
Guido
G
Pierimarchi
Pasquale
P
Bernard
Paola
P
Guarino
Enrico
E
Guadagni
Fiorella
F
Garaci
Enrico
E
D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control / Q000556:secondary*; D008297:Male; D009842:Oligopeptides / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D014611:Vaccination
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D009842:Oligopeptides