Retargeting to EGFR enhances adenovirus infection efficiency of squamous cell carcinoma

Background: Adenovirus-mediated gene therapy has been used for squamous cel l carcinoma of the head and neck (SCCHN), but the in vivo efficacy has been limited by a lack of tissue specificity and low infection efficiency. We a re interested in improving cancer gene therapy strategies using targeted ad enovirus vectors. Objective: To determine if the infection efficiency of adenovirus-mediated gene transfer to SCCHN cells could be enhanced by retargeting to the epider mal growth factor receptor (EGFR), which is known to be overexpressed in th ese tumors. Design: Epidermal growth factor receptor retargeting in SCCHN cells was acc omplished with a bispecific antibody that recognized the knob domain of ade novirus as well as EGFR. Using this retargeting schema, we compared the inf ection efficiency and specificity of unmodified and EGFR-retargeted adenovi rus. Results: Squamous cell carcinoma of the head and neck cell lines were shown to be infected by adenovirus with low efficiency, which is likely because of the low level of adenovirus receptor expressed in the SCCHN cells. Epide rmal growth factor receptor retargeting markedly enhanced transduction in b oth SCCHN cell lines and primary tumor tissue, as indicated by the elevated levels of reporter gene expression. Furthermore, retargeting enhanced infe ction of turner tissue compared with normal tissue from the same patient. Conclusions: Epidermal growth factor receptor retargeting enhanced adenovir us infection of SCCHN cells and, in doing so, augments the potency of the v ector. This modification makes the vector potentially more valuable in the clinical setting.