Adenovirus-mediated gene therapy for head and neck squamous cell carcinomas.
Advanced head and neck squamous cell carcinomas (HNSCCs) have a poor prognosis despite aggressive multimodal therapy. The goal of our study was to test the feasibility of gene transduction as a novel therapy for head and neck cancer. Three human HNSCC cell lines were transduced in vitro with a replication-deficient recombinant adenovirus containing the lacZ marker gene (Ad2/CMV beta gal). Gene transduction efficiency was dependent on multiplicity of infection, duration of exposure to the virus, and viral concentration. Next, the HEp-2 cell line was transduced with an adenoviral vector (Ad.RSVtk) containing the herpes simplex virus thymidine kinase (HSVtk) gene, which, when expressed, sensitizes transduced cells to ganciclovir (GCV). Subsequent administration of GCV resulted in complete tumor cell killing. These results suggest that adenovirus-mediated transfer of HSVtk and administration of GCV has potential as a new therapy for HNSCC.
Goebel
E A
EA
Department of Otolaryngology-Head and Neck Surgery, University of Iowa College of Medicine, Iowa City, USA.
Davidson
B L
BL
Zabner
J
J
Graham
S M
SM
Kern
J A
JA
D000256:Adenoviridae; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D018929:Cell Culture Techniques; D003131:Combined Modality Therapy; D015774:Ganciclovir / Q000627:therapeutic use*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D007830:Larynx / Q000473:pathology; D010610:Pharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D010614:Pharynx / Q000473:pathology; D018139:Simplexvirus; D014059:Tongue / Q000473:pathology; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*
D015774:Ganciclovir