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Head and neck cancer cells are efficiently infected by Ad5/35 hybrid virus
Author(s) -
Suominen Elina,
Toivonen Raine,
Grenman Reidar,
Savontaus Mikko
Publication year - 2006
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.957
Subject(s) - head and neck squamous cell carcinoma , cancer research , genetic enhancement , biology , viral vector , transduction (biophysics) , adenoviridae , microbiology and biotechnology , transgene , gene expression , receptor expression , receptor , cancer , head and neck cancer , gene , recombinant dna , biochemistry , genetics
Background Clinical gene therapy trials using standard Ad5‐based vectors have thus far demonstrated limited efficacy, most likely due to low expression levels of adenoviral receptors on tumor cells. We sought to analyze adenoviral receptor expression levels on primary head and neck squamous cell carcinoma (HNSCC) cells and to determine whether adenoviral retargeting to the CD46 receptor via the Ad5/35 system would increase therapeutic potential for HNSCC. Methods We used flow cytometric analyses to determine adenoviral receptor expression levels on nine primary HNSCC cells collected from cancer patients. Adenoviruses Ad5.LacZ and Ad5/35.LacZ were used to analyze the differences in viral transduction both in vitro and in a HNSCC tumor mouse model. Results Flow cytometric analyses demonstrated uniformly high CD46 expression in all cells studied (85–99%). In contrast, coxsackievirus and adenovirus receptor (CAR) expression was substantially lower and highly variable (1.6–62%). α v integrin expression was between 39–98%. In situ stainings for β‐galactosidase gene expression demonstrated that Ad5/35.LacZ was clearly more effective than Ad5.LacZ in transducing primary HNSCC cells. Quantification of β‐galactosidase expression revealed up to 65 times higher transgene expression from Ad5/35.LacZ than Ad5.LacZ. In vivo , β‐galactosidase expression was detected in a substantial area after a single intratumoral injection of Ad5/35.LacZ, whereas injection with Ad5.LacZ resulted in gene expression only in a few cells. Conclusions Our results demonstrate that the low and variable CAR expression levels limit the therapeutic efficacy of Ad5‐based strategies for HNSCC. In contrast, the effective in vivo transduction capacity of Ad5/35 warrants further development of this vector for the treatment of head and neck cancer. Copyright © 2006 John Wiley & Sons, Ltd.