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

Abstract:

: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.

journal_name

Int J Cancer

authors

Sinibaldi Vallebona P,Rasi G,Pierimarchi P,Bernard P,Guarino E,Guadagni F,Garaci E

doi

10.1002/ijc.20063

keywords:

subject

Has Abstract

pub_date

2004-05-20 00:00:00

pages

70-5

issue

1

eissn

0020-7136

issn

1097-0215

journal_volume

110

pub_type

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