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首页> 外文期刊>Cancer science. >hTERT-promoter-dependent oncolytic adenovirus enhances the transduction and therapeutic efficacy of replication-defective adenovirus vectors in pancreatic cancer cells.
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hTERT-promoter-dependent oncolytic adenovirus enhances the transduction and therapeutic efficacy of replication-defective adenovirus vectors in pancreatic cancer cells.

机译：hTERT启动子依赖性溶瘤腺病毒增强了胰腺癌细胞中复制缺陷型腺病毒载体的转导和治疗功效。

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Adenovirus-mediated gene therapy shows promise for cancer therapy, but transgene expression of replication-defective adenovirus may be low and transient in clinical settings. Recent reports have shown that the use of a conditionally replication-competent adenovirus (CRAd) enhanced the gene transduction of a replication-defective adenovirus vector. The control of tumor-stromal interactions has also been determined to be important in cancer therapy. In this study, we investigated the effect of the human telomerase reverse transcriptase (hTERT)-CRAd, Ad5/3hTERTE1, which possesses the tumor-specific hTERT promoter with the chimeric fiber 5/3, on the transgene expression and therapeutic efficacy of a replication-defective adenovirus vector expressing NK4 under the control of the CMV promoter, Ad-NK4. In addition, we established a new strategy to target both cancer cells and cancer-stromal interactions. Human pancreatic cancer cells were infected with Ad-NK4 and either Ad5/3hTERTE1 (CRAd-combination group) or Ad5/3hTERTLuc (control-combination group). In the CRAd-combination group, Ad-NK4-delivered transgene expression was increased, leading to an enhanced inhibitory effect on the invasion of cancer cells. In in vivo experiments, NK4 expression within tumors and its inhibitory effect on tumor growth, angiogenesis, and metastasis were enhanced in the CRAd-combination group. These results suggest that hTERT-CRAd enhances the transgene expression and therapeutic efficacies of Ad-NK4, possibly through the in-trans replication of Ad-NK4 induced by adenovirus E1 derived from co-infected hTERT-CRAd. This approach may be a promising combination therapy against advanced pancreatic cancer.
机译：腺病毒介导的基因治疗显示出有望用于癌症的治疗，但是复制缺陷型腺病毒的转基因表达在临床环境中可能较低且短暂。最近的报道表明，使用有条件复制能力的腺病毒（CRAd）可以增强复制缺陷型腺病毒载体的基因转导。还已经确定控制肿瘤-基质相互作用在癌症治疗中很重要。在这项研究中，我们调查了人类端粒酶逆转录酶（hTERT）-CRAd，Ad5 / 3hTERTE1（其具有与嵌合纤维5/3结合的肿瘤特异性hTERT启动子）对转基因表达和复制的治疗功效的影响在CMV启动子Ad-NK4的控制下表达NK4的缺陷型腺病毒载体。另外，我们建立了针对癌细胞和癌症-基质相互作用的新策略。用Ad-NK4和Ad5 / 3hTERTE1（CRAd组合组）或Ad5 / 3hTERTLuc（对照组）感染人胰腺癌细胞。在CRAd组合组中，Ad-NK4递送的转基因表达增加，导致对癌细胞侵袭的抑制作用增强。在体内实验中，CRAd联合组增强了肿瘤内NK4的表达及其对肿瘤生长，血管生成和转移的抑制作用。这些结果表明，hTERT-CRAd可能通过由共感染hTERT-CRAd衍生的腺病毒E1诱导的Ad-NK4的反式复制增强了Ad-NK4的转基因表达和治疗效果。该方法可能是针对晚期胰腺癌的有前途的联合疗法。

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