Synergistic Radiosensitization Effect of Combination of CpG ODNs and Herceptin

• Main Authors: Chieh-Han Yang, 楊杰翰
• Other Authors: 季昭華
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/49462320761461204706

碩士 === 國立臺灣大學 === 獸醫學研究所 === 94 === We hypothesized that targeted therapy with antibody in combination of CpG oligodeoxynucleotides (ODN) would further activate NK cells and resulte in strong radiosensitization effect. This hypothesis has never been proved. The effects of blocking HER2 by Herceptin in combination of CpG ODN on radiosensitization effect were evaluated in this experiment. A BALB/c murine colon carcinoma line overexpressing human HER2/neu, CT26HER2/neu, was used in our experiment. When tumor reaches 4mm in diameter, CpG ODN 100μ intratumorally and Herceptin 200μg intraperitoneally were injected per mice in consecutive three days. Radiation of 800cGy to tumor was performed on day 4. Tumor growth curve, survival rate, TCD50, and tumor rechallenge were studied. In vitro radiosensitization effects were investigated by coculture with CT26HER2/neu with PBMC with or without CpG and Herceptin before radiation. Cytokine profiles changes were also evaluated. The combination of CpG and Herceptin before radiation retard tumor growth and prolong survival of mice in comparison with CpG only or Herceptin only. The long term tumor control rate was increased. In vitro experiments demonstrated that the combination of CpG and Herceptin stimulate more IFN-r (160pg/ml) than CpG only (130pg/ml) or Herceptin only (27pg/ml) on mice splenocytes, and increase the cell lysis percentage caused by RT (44.7%) compared with CpG only (29.94%). Our study indicated that the combination of CpG ODN and Herceptin sensitize CT26HER2/neu to radiation-induced apoptosis. Co-injection CpG and Herceptin may effectively enhance radiotherapy efficacy.