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Gene therapy for head and neck squamous cell carcinoma – imaging a cancer‐selective, selective, systemically‐administered agent
Author(s) -
Edward C.,
Nick L.,
Ghassan A.,
Andreas S.,
Georges V.
Publication year - 2007
Publication title -
clinical otolaryngology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.914
H-Index - 68
eISSN - 1749-4486
pISSN - 1749-4478
DOI - 10.1111/j.1749-4486.2007.01568_3.x
Subject(s) - sodium iodide symporter , medicine , cancer research , genetic enhancement , head and neck squamous cell carcinoma , head and neck cancer , cancer , in vivo , thyroid cancer , transfection , pathology , gene , symporter , biology , microbiology and biotechnology , transporter , biochemistry
. Cancer gene therapy for head and neck squamous cell carcinoma (HNSCC) has been limited by difficulties delivering and monitoring expression of the therapeutic gene in vivo . By utilising a nanoparticle vector complexed with the sodium iodide symporter (responsible for the thyroid gland's ability to concentrate iodide) we demonstrate an agent which can be used to both monitor and treat HNSCC and its metastases. Method. Polypropylenimine dendrimers (DAB‐16) were complexed with a plasmid encoding the sodium iodide symporter (NIS). The complex was injected intra‐tumorally (IT) or intravenously (IV) into both nude and immune competent mice bearing 1 or more subcutaneous HNSCC. 99m Technicium was injected intra‐peritoneally and whole‐body SPECT‐CT imaging of the mice was performed. Quantitative real time polymerase chain reaction (qRT‐PCR) of biopsied tumour samples and other organs was used to confirm areas of gene expression. Results. SPECT‐CT demonstrated cancer specific and selective expression of the NIS gene in all tumours following both IT and IV administration in nude and immune competent mice. The effective transfection of the gene was confirmed by qRT‐PCR of the tumour tissue. The tumour specificity was shown to be due to the nanoparticle vector. Conclusion. This is the first time that cancer‐specific gene transfer has been reproducibly achieved using a systemically administered agent. This methodology allows the treatment of HNSCC with 131 I or other ‘anti‐cancer’ genes, such as p53 whilst allowing in vivo monitoring of gene expression. Metastatic or occult tumours could also be targeted without prior knowledge of their site.