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首页> 美国政府科技报告 >Antiangiogenic Gene Therapy for Breast Cancer Using Targeted Recombinant Adenovirus
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Antiangiogenic Gene Therapy for Breast Cancer Using Targeted Recombinant Adenovirus

机译：靶向重组腺病毒对抗乳腺癌的抗血管生成基因治疗

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We tested the expression of NC2 in HeLa cells and generated an El- expression HeLa cell line for the rescue for NG2 targeted adenovirus. Three attempts at virus rescue using NG2 targeted plasmid failed to yield targeted adenovirus. This was not due to a problem with the rescue procedure as we were able to rescue an identical virus without targeting function. We later confirmed by synthesized fluorescence labeled NG2 binding peptide that NC2 binding peptide did not bind to HeLa cells indicating the NG2 binding peptide selected by phage display is not suitable for adenovirus targeting. Therefore, we switched our project to transcription targeting through the use of tumor specific telomerase reverse transcriptase (TERT) promoter to control the replication of recombinant adenovirus- conditionally replicative adenovirus (CRAD). CRAD is an attractive anticancer agent as it can selectively replicate in tumor cells and amplify the input virus dose. CRAD adenovirus, Adv-TERTp-ElA, we constructed replicated severely attenuated in TERT-negative cells, but it replicated almost as efficiently as wild-type adenovirus in TERT-positive cells. Adv-TERTp-ElA caused TERT-positive, but not TERT-negative, cells die. This virus replicated well in tumor xenograft and caused substantial tumor necrosis without hepato- toxicity. These results indicate that Adv-TERTp-ElA can be potentially utilized as a cancer treatment agent.

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