Selective infection and cytolysis of human head and neck squamous cell carcinoma with sparing of normal mucosa by a cytotoxic herpes simplex virus type 1 (G207)

Citation
Jf. Carew et al., Selective infection and cytolysis of human head and neck squamous cell carcinoma with sparing of normal mucosa by a cytotoxic herpes simplex virus type 1 (G207), HUM GENE TH, 10(10), 1999, pp. 1599-1606
Citations number
13
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
HUMAN GENE THERAPY
ISSN journal
1043-0342 → ACNP
Volume
10
Issue
10
Year of publication
1999
Pages
1599 - 1606
Database
ISI
SICI code
1043-0342(19990701)10:10<1599:SIACOH>2.0.ZU;2-Q
Abstract
This study evaluates inhibition of human squamous cell carcinomas (SCCs) by a replication-competent multimutated herpes simplex virus type 1 (G207). I nfectivity and cytotoxicity of the G207 virus were evaluated in vitro in se ven human SCC cell lines. In vivo effects of the G207 virus on human tumor xenografts in an athymic rat model were then investigated by injecting esta blished tumors with 1 x 10(7) virus particles and monitoring tumor growth. In addition, oral cavity tumors in immunocompetent hamster were infected wi th the G207 virus by selective intraarterial perfusion and the tumor respon se was monitored, In vitro studies demonstrated infection rates, measured 2 4 hr after exposure, exceeding 40% at an MOI of 2 in five of seven human SC C cell lines. Cytotoxic effects, as measured by percent cell death on day 5 , exceeded 90% in five of seven SCC cell lines. In vivo inhibition of tumor growth in an athymic rat model was seen (p < 0.005) and in two of the cell lines a complete clinical response was seen in 12 of 14 tumors, In the ham ster model, selective intraarterial perfusion with G207 virus showed select ive infection of the tumor cells, with sparing of the adjacent normal mucos a, which leading to significant suppression of tumor growth (p < 0.005). Th e G207 virus displayed efficient and selective cytotoxicity and tumor growt h inhibition against human SCC and may prove useful as a therapeutic agent for head and neck SCC.