Targeting advanced non small cell lung cancer in vivo by pulmonary surfactant -adenovirus-mediated gene transfer

Pulmonary Surfactant has been used as a carrier to deliver a治疗病毒to dysfunctional lung cells that intricate lung structure内的局部功能性lung cells。为了调查在体内增强脉搏作用的治疗病毒的治疗性植入的有效性，以目标为先进的非小细胞肺癌，我们开发了一种重组腺病毒，其诱导仅在肺癌细胞死亡的细胞中被注射到先进的肺癌模型中的腺病毒，并被注射到高级肺癌模型中的腺病毒中，通常有或没有生长因子。一种治疗腺病毒，它只在肺癌细胞中死亡的诱导体是由与细胞毒性E1 A结合的肺癌特定启动子组成的。此腺病毒被直接插入到KRAS或KRASLung c\模型中（CCSP-rtTA/Tet-op、K-Ras 4 bG 12 D bitransgenic mice或CCSP-rtTA/Tet-op、K-Ras 4 bG 12 D、p53-tripletrangenic mice）中的存在/absence of pulmonary surfactant。Intracheally-injection治疗腺病毒与脉冲表面活性剂扩散到空中，如在肺癌模型老鼠中开发的肺肿瘤和引起的减少肺肿瘤的平均区域。在没有脉搏性表面活性剂的情况下，治疗性腺病毒只能传播到空中，并且在肿瘤减少中有10个时间没有效果。在这里，我们演示了一种激素活性剂是一种有效的工具，可以在体内传递体外治疗病毒，以治疗高级肺癌。

Pulmonary surfactant has been used as a carrier to deliver a therapeutic virus to dysfunctional lung cells that reside within an intricate lung structure. To investigate whether pulmonary surfactant enhances the efficacy of intratracheal instillation of a therapeutic virus to target advanced non small cell lung cancer in vivo, we developed a recombinant adenovirus that induces cell death only in lung cancer cells and injected the adenovirus into an advanced lung cancer model mouse intratracheally with or without surfactant. A therapeutic adenovirus that induces cell death only in lung cancer cells was constructed by combining a lung cancer specific promoter fused to cytotoxic E1A. This adenovirus was intratracheally injected into the KRAS or KRASlung cancer model mice (CCSP-rtTA/Tet-op・K-Ras4bG12D bitransgenic mice or CCSP-rtTA/Tet-op・K-Ras4bG12D・p53- tripletransgenic mice) in the presence/absence of pulmonary surfactant. Intratracheally-injected therapeutic adenovirus with pulmonary surfactant spread to airways as well as to the alveolar region of the lung and caused reduction of lung tumors developed in the lung cancer model mice. The therapeutic adenovirus without pulmonary surfactant spread only to airways and had ten times less effectiveness in tumor reduction. Here, we demonstrate that pulmonary surfactant is an efficient tool to intratracheally deliver a therapeutic virus to treat advanced lung cancer in vivo.