Non-small cell lung cancer as a target disease for herpes simplex type 1 thymidine kinase-ganciclovir gene therapy.
Lung cancer is a group of diseases that are difficult to cure and new treatment modalities, like gene therapy are actively tested to find alternatives for currently used strategies. Herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) method is one of the most frequently utilized forms of gene therapy and it has been tested on lung cancer, but no systematic study with comparison of different lung cancer types has been published. In this study, we examined in vitro and in vivo how good targets non-small cell lung cancer (NSCLC) cell lines representing adenocarcinoma, squamous cell lung cancer and large cell lung cancer are for adenovirus-mediated HSV-TK/GCV gene therapy. By using an adenovirus vector carrying a fusion gene of HSV-TK and green fluorescent protein (GFP), we found that: a) adenoviruses were efficient gene transfer vehicles for all types of NSCLCs; b) all adenocarcinoma and large cell lung cancer cells were good targets for HSV-TK/GCV therapy, whereas one of the squamous cell carcinoma cell lines was not responsive to the treatment; c) bystander effect played a major role in the success of this gene therapy form; d) subcutaneous tumors representing all three NSCLC types were efficiently treated with adenovirus-mediated HSV-TK/GCV gene therapy. In summary, this form of gene therapy appeared to be efficient treatment for human NSCLC and these results warrant further studies with primary lung cancer cells and orthotopic lung tumor models.
Määttä
Ann-Marie
AM
Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland.
Tenhunen
Anni
A
Pasanen
Tiina
T
Meriläinen
Outi
O
Pellinen
Riikka
R
Mäkinen
Kimmo
K
Alhava
Esko
E
Wahlfors
Jarmo
J
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D024201:Bystander Effect; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000628:therapy*; D003131:Combined Modality Therapy; D015774:Ganciclovir / Q000494:pharmacology*; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000235:genetics / Q000628:therapy; D013937:Thymidine Kinase / Q000235:genetics*; D014161:Transduction, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D013937:Thymidine Kinase; D015774:Ganciclovir