Study Of The Potential Antitumor Activities In Hepatocellular Carcinoma By Oncolytic Adenovirus Armed With LAPTM4B-24

Malignant tumor was a multi-gene mutation disease caused by both genetic andenvironmental factors. The traditional cancer treatments, such as surgery,chemotherapy and radiotherapy, had limited efficacies. Therefore, it was importantto develop other new therapies, such as gene therapy and virotherapy.Gene therapy was to insert wide-type genes into the genome aimed to replacemutated genes. Virotherapy belonged to preclinical cancer treatments to modifyviruses into cancer-treating agents by retargeting viruses to cancerous cells, whilenormal cells remained relatively undamaged. Oncolytic adenoviruses, also calledconditionally replicative adenoviruses, belonged to these agents. They were a kindof promising anti-cancer agent, which replicated selectively in cancer cells andresulted in cancer-specific cytotoxicity. But neither gene therapy nor virotherapywas effective enough when it was used alone. Thus, tumor targetinggene-virotherapy was developed.. Tumor targeting gene-virotherapy combined gene therapy (therapeutic genes)and virotherapy (oncolytic adenovirus) to treat cancer. Not only the transferefficiency of the therapeutic gene could be improved by oncolytic adenovirus, but also the effectiveness of oncolytic adenovirus-based killing tumor cells could beenhanced with the help of the therapeutic genes.Oncolytic adenovirus AdCN205was previously generated in our lab. It wasdeleted at24bp (CR2E1A)，replaced6.7K/gp19K of E3genes with therapeuticgene, and had an inserted hTERT gene promoter to control transcription of E1Agenes to become a safer tumour-specific vector.LAPTM4B was a new gene discovered in2000, which encoded two proteins:LAPTM4B-35and LAPTM4B-24. LAPTM4B-35protein was significantlyupregulated in a wide variety of cancers, which had relationship with grading,invasion and metastasis, and prognosis of hepatomacellular carcinoma.LAPTM4B-24protein had some features of tumor-suppressing genes, such asinhabiting colony formation of liver cancer cells. To study its suppressing role inhepatocellular carcinoma and the underling mechanism, AdCN205was insertedwith the cNDA encoding LAPTM4B-24, then generatingAdCN205-LAPTM4B-24.The results showed that AdCN205-LAPTM4B-24replicated selectively in theliver cancer cells, and LAPTM4B-24could be expressed effectively. AdCN205-LAPTM4B-24displayed an anti-tumor efficacy both in vitro and invivo.In conclusion, AdCN205-LAPTM4B-24was proved to be a potent and safebiological agent for cancer treatment.