Development of tumor specific viralvector and application for gene therapy against human pancreatic cancer

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We investigated the correlation between several cancer associated genes and histopathological features in several cancers, and reported that high expression of RCAS1 gene correlated with tumor progression and predicted poor outcome in carcinomas of the gallbladder, the esophagus, the bile duct, and the pancreas. Especially in pancreatic cancer, RCAS1 expression was very frequent. Our data suggested that RCAS1 could be a potential target for gene therapy against pancreatic cancer. We also reported the investigation of gene therapy for pancreatic cancer. As the activation of ras protooncogene was important for progression of pancreatic cancer, we made a replication-deficient recombinant adenovirus expressing a dominant negative ras mutant, which reduced the activation of endogenous ras, driven by the carcinoembryonic antigen promoter (AdCEA-N116Y). We examined the effect of AdCEA-N116Y on the metastatic growth of pancreatic cancer cell line PCI-43 in liver, which was generated by tumor injection into the spleen of nude mice. The results showed that AdCEA-N116Y effectively reduced the number of metastatic colonies without any complication. Thus, N116Y can selectively suppress the metastatic growth of pancreatic tumor cell by using the CEA promoter-driven adenovirus vector indicating that N116Y gene therapy may be potentially useful for the treatment of pancreatic cancer patients with liver micrometastasis