標定活化前驅藥物之載體以便進行選擇性的癌症治療

增加化療的專一性能改善癌症治療的效率,為了達到這樣的目的，本論文設計兩個策略，以便將前驅藥物活化酵素(乙型葡萄糖苷酸酵素)專一性標定到腫瘤的位置。一為利用半抗原標定前驅藥物活化酵素，與半抗原標定細胞激素的合併雞尾酒療法達到選擇性腫瘤治療?咱t一則利用能座落並放大於腫瘤區域的細菌(表現前驅藥物活化酵素)以便進行選擇性的癌症治療。我們的結果證實：(1)功能性的DNS ScFv能穩定表現於老鼠的CT-26大腸癌細胞上、半抗原(DNS)經由polyethylene glycol能與乙型葡萄糖苷酸酵素與細胞激素(IL-2)形成共價鍵結，而且DNS修飾後的治療分子能專一性標定到表現DNS ScFv的腫瘤細胞上，達到合併性的選擇性療法，很明顯地延緩腫瘤的生長。(2)能活化前驅藥物的冷光菌喜愛座落並放大於裸鼠所帶之人類肺癌(CL1-5)的腫瘤區域，相較於單純給予細菌或前驅藥物處理的組別，系統性給予前驅藥物活化細菌合併前驅藥物處理的組別，很明顯地延緩了腫瘤的生長(p<0.005)，亦證實這樣的前驅藥物活化細菌能用於選擇性的癌症治療。

關鍵字

前驅藥物療法；半抗原標定前驅藥物活化酵素；乙型葡萄糖苷酸酵素；標定腫瘤之前驅藥物活化細菌

並列摘要

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.

並列關鍵字

prodrug therapy ； Hapten-taregted prodrug activating enzyme ； beta-glucuronidase ； Tumor-targeting prodrug activating bacteria

參考文獻

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標定活化前驅藥物之載體以便進行選擇性的癌症治療

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