title: Possible novel therapy for malignant gliomas with secretable trimeric TRAIL.
abstract: Malignant gliomas are the most common primary brain tumors. Despite intensive clinical investigation and many novel therapeutic approaches, average survival for the patients with malignant gliomas is only about 1 year. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown potent and cancer-selective killing activity and drawn considerable attention as a promising therapy for cancers, but concerns over delivery and toxicity have limited progress. We have developed a secretable trimeric TRAIL (stTRAIL) and here evaluated the therapeutic potential of this stTRAIL-based gene therapy in brain tumors. An adenovirus (Ad-stTRAIL) delivering stTRAIL was injected into intra-cranial human glioma tumors established in nude mice and tumor growth monitored using the magnetic resonance imaging (MRI). Ad-stTRAIL gene therapy showed potent tumor suppressor activity with no toxic side effects at therapeutically effective doses. When compared with 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a conventional therapy for malignant gliomas, Ad-stTRAIL suppressed tumor growth more potently. The combination of Ad-stTRAIL and BCNU significantly increased survival compared to the control mice or mice receiving Ad-stTRAIL alone. Our data indicate that Ad-stTRAIL, either alone or combined with BCNU, has promise as a novel therapy for malignant gliomas.
authors.affiliation: Biopharmaceutical Research Laboratories of Dong-A Pharmaceutical Co, Ltd, Kyunggi-Do, Korea.
authors.forename: Moonsup
authors.initials: M
authors.lastname: Jeong
authors.forename: Yong-Sam
authors.initials: YS
authors.lastname: Kwon
authors.forename: Soon-Hye
authors.initials: SH
authors.lastname: Park
authors.forename: Chae-Young
authors.initials: CY
authors.lastname: Kim
authors.forename: Sin-Soo
authors.initials: SS
authors.lastname: Jeun
authors.forename: Kang-Won
authors.initials: KW
authors.lastname: Song
authors.forename: Yong
authors.initials: Y
authors.lastname: Ko
authors.forename: Paul D
authors.initials: PD
authors.lastname: Robbins
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
authors.forename: Byong-Moon
authors.initials: BM
authors.lastname: Kim
authors.forename: Dai-Wu
authors.initials: DW
authors.lastname: Seol
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002330:Carmustine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D009368:Neoplasm Transplantation; D015996:Survival Rate; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage*; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D002330:Carmustine