Generation and Characterization of Monoclonal Antibodies Against Lung cancer

• Main Authors: Hui-Yu Chen, 陳慧宇
• Other Authors: 吳漢忠
• Format: Others
• Language: en_US
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/24677843427424837681

碩士 === 國立臺灣大學 === 口腔生物科學研究所 === 96 === Lung cancer is the leading cause of cancer deaths, accounting for one third of all deaths from cancer worldwide. In the United States, accounting for about 29% of all cancer deaths, are expected to happen in 2008. In Taiwan, lung cancer is the first most common cancer and the death rate is the highest among all cancers, accounting for approximately 19.7% of all cancer deaths in 2006. Lung cancer is classified clinically as small (SCLC) (15-20%) or non-small cell lung cancer (NSCLC) (80-85%) for the purposes of treatment. Current treatment options include surgical resection, platinum-based doublet chemotherapy, and radiation therapy alone or in combination. However, there are many side effects and drug resistance of these treatments. Despite these therapies, the disease is rarely curable and the prognosis is poor, with an overall 5-year survival rate of only 15%. Because monoclonal antibodies (mAbs) have the ability to target tumours, and hence enables them to improve the selectivity of other types of anticancer agent. Therapeutic antibodies have established themselves as one of the most important and fastest growing classes of drugs for cancer. In this study, we have generated 12 mAbs which were specifically against CL1-5 and did not cross-react to normal cells including NNM cells, HUVEC, PBMC and normal human tissues. Four mAbs LC-Ab 1-7, LC-Ab 2-37, LC-Ab 8-5 and LC-Ab 9-5 exhibited high specificities against CL1-5. Therefore, we focused on these 4 mAbs to further characterize their biological properties. In Western blot analysis, LC-Ab 1-7, LC-Ab 2-37 and LC-Ab 4-12 recognize a protein with M.W. 60 kDa, 120 kDa and 58 kDa, respectively. These target proteins were also identified in other cancer cell line, including SAS and MDA-MB 231 by flow cytometric analysis. Furthermore, LC-Ab 2-37, LC-Ab 8-5 and LC-Ab 9-5 can induce apoptosis of cancer cells using flow cytometric analysis. Results from immunohistochemical staining of human surgical specimen sections by LC-Ab 1-7, LC-Ab 2-37, LC-Ab 8-5 and LC-Ab 9-5 indicated that these mAbs might be promising to be applied in the diagnosis and treatment for NSCLC. According to these data, the target proteins of these mAbs and their possible usage as tumor markers and development of Ab-targeted chemotherapy is warranted.