Selective gene delivery to head and neck cancer cells via an integrin targeted adenoviral vector

In vivo cancer gene therapy approaches for squamous cell carcinoma of the h ead and neck (SCCHN) based on adenoviral vector-mediated gene delivery have been limited by the suboptimal efficacy of gene transfer to tumor cells. W e hypothesized that this issue was due to deficiency of the primary adenovi ral receptor, the coxsackie-adenovirus receptor (CAR), on the tumor targets . Studies of CAR levels on SCCHN cell lines confirmed that their relative r efractoriness to the adenoviral vector was based on this deficiency. To cir cumvent this deficiency, we applied an adenoviral vector targeted to a tumo r cell marker characteristic of SCCHN, In this regard, integrins of the alp ha(2)beta(1) and alpha(3)beta(1) class are frequently overexpressed in SCCH N. Furthermore, these integrins recognize the RGD peptide motif, On this ba sis, we applied an adenoviral vector genetically modified to contain such a peptide within the HI loop of the fiber protein as a means to alter viral tropism, Studies confirmed that the CAR-independent gene delivery achieved via this strategy allowed enhanced gene transfer efficiencies to SCCHN tumo r cells. Importantly, this strategy could achieve preferential augmentation of gene transfer in tumor cells compared with normal cells. The ability to achieve enhanced and specific gene transfer to tumor cells via adenoviral vectors has important implications for gene therapy strategies for SCCHN an d for other neoplasms in general.