title: Gene therapy for oral squamous cell carcinoma with IAI.3B promoter-driven oncolytic adenovirus-infected carrier cells.
abstract: Although replication-competent oncolytic viral vectors have been developed to improve antitumor activity, the generation of high titers of neutralizing antibodies inhibits repetitive viral infection. Many studies have reported that oncolytic virus-infected carrier cells can overcome this viral induced immunogenicity. However, the effects of oncolytic virus-infected carrier cells in human oral squamous cell carcinoma (OSCC) have not yet been examined. In the present study, simulating the clinical trial, we examined the antitumor activity of carrier cells infected with oncolytic adenovirus AdE3-IAI.3B in human OSCC. IAI.3B was highly activated in OSCC cells but not in normal cells. AdE3-IAI.3B killed OSCC cells in vitro but not normal cells. AdE3-IAI.3B-infected A549 carrier cells eradicated OSCC GFP-SAS tumors in nude mice. Anti-adenovirus neutralizing antibodies completely blocked the antitumor effect of AdE3-IAI.3B but did not block that of carrier cells. After the induction of anti-adenoviral CTL responses by immunization of adenovirus, administration of carrier cells induced complete regression of murine squamous cell carcinoma SCC7 tumors. Adenovirus-GM-CSF augmented the antitumor effect of carrier cells. The IAI.3B-driven oncolytic adenovirus-infected carrier cell system might prove useful in the treatment of OSCC and clinical trials of it should be conducted in the near future.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hamada
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Hyodo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.forename: Kenzaburo
authors.initials: K
authors.lastname: Tani
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Goda
authors.forename: Koh-Ichi
authors.initials: K
authors.lastname: Nakashiro
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hamakawa
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002478:Cells, Cultured; D015316:Genetic Therapy; D005822:Genetic Vectors; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology; D011401:Promoter Regions, Genetic; D023041:Xenograft Model Antitumor Assays