Targeting prodrug-activating vectors for selectivecancer therapy

• Main Authors: Chiu-Min Cheng, 鄭秋敏
• Other Authors: Tian-Lu Cheng
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/01846110593367936379

博士 === 高雄醫學大學 === 醫學研究所 === 96 === Increasing the specificity of chemotherapy may improve the efficacy of cancer treatment. Toward this aim, two strategies were designed to specific delivery prodrug activating enzyme (??-glucuronidase) to tumors. One is combination cancer therapy by Hapten-Targeted Prodrug –Activating Enzymes and Cytokines; another is bacteria-directed enzyme prodrug therapy. Our results demonstrated that (1) Functional DNS scFv could be stably expressed on CT-26 colon cancer cells both in vitro and in vivo. Dansyl moieties were covalently attached to recombinant ??-glucuronidase (?浤) and interleukin 2 (IL-2) via a flexible poly (ethylene glycol) linker to form DNS-PEG-?浤 and DNS-PEG-IL-2 conjugates. The dansyl-modified therapeutic agents can be selectively delivered to dansyl ScFv receptors in vitro and in vivo and allowing combination therapy of dansyl ScFv-modified tumors. (2) The prodrug activating luminescence bacteria preferentially localized and replicated within CL1-5 human lung tumors in mice. In comparison with bacteria alone, active drug (9AC) or prodrug (9ACG) treatment, combined systemic administration of DH5??-lux/?浤 followed by 9ACG prodrug treatment significantly (p<0.005) delayed the growth of CL1-5 tumors, the prodrug activating bacteria may be useful for selective cancer chemotherapy.