Abstract 5701: Targeting KRAS lung cancer in vivo by pulmonary surfactant-mediated gene transfer

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL 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 KRAS lung cancer in vivo, we developed a recombinant adenovirus that induces cell death only in lung cancer cells and injected the adenovirus into a KRAS 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 cancer specific hTERT promoter fused to CEBPα with a modified lung specific CC10 promoter fused to cytotoxic E1A. CEBPα is induced only in cancer cells and activates the CC10 promoter, which in turn induces cytotoxic E1A, and causes cell death only in lung cancer cells in vitro. This adenovirus was intratracheally injected into the KRAS lung cancer model mice (CCSP-rtTA/Tet-op-K-Ras4bG12D bitransgenic 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 KRAS lung cancer model mouse. 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 KRAS lung cancer in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5701. doi:1538-7445.AM2012-5701