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 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.

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.