Development of cancer specific viral vector for carcinoma by inducing the plural genes

我们研究了在几种器官肿瘤中表达的肿瘤特异性抗原。胰腺癌组织中RCAS1基因阳性率为90%。此外，RCAS1基因过表达与胰腺癌、肝外胆管癌、食道癌患者的预后相关。小窝蛋白-1的表达也与胰腺癌患者的预后有关。我们构建了由RCAS1启动子(Ad RCAS1-KLAK2，Ad RCAS1-Bax)或SCCA启动子(Ad SCCA-KLAKLAK2)驱动的复制缺陷重组KLAKLAK2或Bax重组腺病毒。我们发现，KLAKLAK2的表达和生长抑制都是SCCA阳性的癌细胞所特有的，而在人正常细胞系中，感染后没有观察到生长抑制。

We studied the cancer specific antigens expressed in the several organ tumors. In pancreatic cancer, 90% were positive for RCAS1 gene. Moreover, overexpression of RCAS1 gene was correlated with the prognosis of patients with pancreatic cancer, extrahepatic bile duct carcinoma and esophageal cancer. Caveolin-1 expression was also correlated with with the prognosis of patients with pancreatic cancer.We made a replication-deficient recombinant KLAKLAK2 or Bax adenovirus driven by the RCAS1promoter (Ad RCAS1-KLAKLAK2, Ad RCAS1-Bax) or the SCCA promoter (Ad SCCA-KLAKLAK2). We demonstrated that the expression of KLAKLAK2 and growth inhibition were all specific to the cancer cell lines that were SCCA positive, whereas no growth retardation was observed in human normal cell lines after Ad SCCA-KLAKLAK2 infection.