Treatment and Mechanism Study of Immunomodulatory Gene Therapy in Orthotopic Liver Tumor

• Main Authors: Hao-Wei Cheng, 鄭皓薇
• Other Authors: 黃麗華
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/77977981714697922322

碩士 === 國立臺灣大學 === 微生物學研究所 === 94 === Hepatocellular carcinoma (HCC) is a worldwide disease, and is one of the leading cancers in Taiwan. Traditional therapies, such as surgery or chemotherapy, were effective only on small tumors or non-metastatic tumors. Thus, searching for new therapeutic strategies has become a topic of intensive research recently. In our laboratory, we have used gene therapy strategies to treat orthotopic hepatocellular carcinoma. Mouse hepatoma cells BNL were inoculated in the liver lobe of BALB/c mice to generate orthotopic liver tumor. Then, adenoviruses carrying IL-12 gene or combination of IL-12 and GM-CSF genes were used to treat tumors seven days after tumor cells inoculation. The results showed that both treatments significantly inhibited tumor growth, but the therapeutic effects of combination therapy were better than IL-12 monotherapy. The most important effector cells involved in the IL-12 treatment were NK cells, whereas those in the combination therapy were NKT cells and CD8 T cells. In the second part, we employed Sindbis viral vector, which could express high level of heterologous genes in mammalian cells, to direct tomor-associated antigen (TAA) expression and performed TAA-based immunotherapy. CT26 cells expressing tumor antigen mAFP were inoculated in the liver lobe of BALB/c mice to generate liver tumor. Seven days after tumor inoculation, mice were immunized intramuscularly with Sindbis virus expressing CRT-tmAFP, VP22-tmAFP or mAFP for three constituitive days. The results indicated that fusion of CRT or VP22 with mAFP induced significant immunity against mAFP-expressing tumors. Further studies are still needed to improve the strategy in the future.