Retargeting to EGFR enhances adenovirus infection efficiency of squamous cell carcinoma.
BACKGROUND
Adenovirus-mediated gene therapy has been used for squamous cell 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 are interested in improving cancer gene therapy strategies using targeted adenovirus vectors.


OBJECTIVE
To determine if the infection efficiency of adenovirus-mediated gene transfer to SCCHN cells could be enhanced by retargeting to the epidermal growth factor receptor (EGFR), which is known to be overexpressed in these tumors.


METHODS
Epidermal growth factor receptor retargeting in SCCHN cells was accomplished with a bispecific antibody that recognized the knob domain of adenovirus as well as EGFR. Using this retargeting schema, we compared the infection efficiency and specificity of unmodified and EGFR-retargeted adenovirus.


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. Epidermal growth factor receptor retargeting markedly enhanced transduction in both SCCHN cell lines and primary tumor tissue, as indicated by the elevated levels of reporter gene expression. Furthermore, retargeting enhanced infection of tumor tissue compared with normal tissue from the same patient.


CONCLUSIONS
Epidermal growth factor receptor retargeting enhanced adenovirus infection of SCCHN cells and, in doing so, augments the potency of the vector. This modification makes the vector potentially more valuable in the clinical setting.
Blackwell
J L
JL
Department of Medicine, University of Alabama at Birmingham, 35294, USA.
Miller
C R
CR
Douglas
J T
JT
Li
H
H
Reynolds
P N
PN
Carroll
W R
WR
Peters
G E
GE
Strong
T V
TV
Curiel
D T
DT
D000256:Adenoviridae / Q000235:genetics*; D018033:Antibodies, Bispecific; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006367:HeLa Cells / Q000821:virology; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D018033:Antibodies, Bispecific; D011993:Recombinant Fusion Proteins; D066246:ErbB Receptors; D001616:beta-Galactosidase