title: Cancer gene therapy by IL-12 gene delivery using liposomal bubbles and tumoral ultrasound exposure.
abstract: Interleukin-12 (IL-12) gene therapy is expected to be effective against cancers because it primes the immune system for cancer cells. In this therapy, it is important to induce IL-12 gene expression in the tumor tissue. Sonoporation is an attractive technique for developing non-invasive and non-viral gene delivery systems, but simple sonoporation using only ultrasound is not an effective cancer gene therapy because of the low efficiency of gene delivery. We addressed this problem by combining ultrasound and novel ultrasound-sensitive liposomes (Bubble liposomes) which contain the ultrasound imaging gas perfluoropropane. Our previous work showed that this is an effective gene delivery system, and that Bubble liposome collapse (cavitation) is induced by ultrasound exposure. In this study, we assessed the utility of this system in cancer gene therapy using IL-12 corded plasmid DNA. The combination of Bubble liposomes and ultrasound dramatically suppressed tumor growth. This therapeutic effect was T-cell dependent, requiring mainly CD8(+) T lymphocytes in the effector phase, as confirmed by a mouse in vivo depletion assay. In addition, migration of CD8(+) T cells was observed in the mice, indicating that the combination of Bubble liposomes and ultrasound is a good non-viral vector system in IL-12 cancer gene therapy.
authors.affiliation: Department of Biopharmaceutics, School of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.forename: Eisuke
authors.initials: E
authors.lastname: Namai
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oda
authors.forename: Norihito
authors.initials: N
authors.lastname: Nishiie
authors.forename: Shota
authors.initials: S
authors.lastname: Otake
authors.forename: Risa
authors.initials: R
authors.lastname: Koshima
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Taira
authors.forename: Naoki
authors.initials: N
authors.lastname: Utoguchi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Negishi
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000628:therapy*; D004247:DNA / Q000008:administration & dosage*; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D018664:Interleukin-12 / Q000235:genetics*; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000628:therapy*; D010957:Plasmids / Q000008:administration & dosage; D014162:Transfection; D014465:Ultrasonics
chemical_list: D008081:Liposomes; D018664:Interleukin-12; D004247:DNA