title: Tat-PTD-modified oncolytic adenovirus driven by the SCG3 promoter and ASH1 enhancer for neuroblastoma therapy.
abstract: Secretogranin III (SGC3) belongs to the granin family and is highly expressed in endocrine and neural tissues. The human SCG3 promoter has not yet been characterized. We identified that a 0.5-kb DNA fragment upstream of the SCG3 gene can selectively drive transgene expression in neuroblastoma cell lines. The strength of transgene expression was further increased, with specificity maintained, by addition of the human achaete-scute complex homolog 1 (ASH1) enhancer. We developed an oncolytic serotype 5-based adenovirus, in which the SCG3 promoter and ASH1 enhancer drive E1A gene expression. The virus was further modified with a cell-penetrating peptide (Tat-PTD) in the viral capsid, which we have previously shown results in increased adenovirus transduction efficiency of many neuroblastoma cell lines. The virus, Ad5PTD(ASH1-SCG3-E1A), shows selective and efficient killing of neuroblastoma cell lines in vitro, including cisplatin-, etoposide-, and doxorubicin-insensitive neuroblastoma cells. Furthermore, it delays tumor growth and thereby prolonged survival for nude mice harboring subcutaneous human neuroblastoma xenograft. In conclusion, we report a novel oncolytic adenovirus with potential use for neuroblastoma therapy.
authors.affiliation: Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala SE-75185, Sweden.
authors.forename: Chuan
authors.initials: C
authors.lastname: Jin
authors.forename: Di
authors.initials: D
authors.lastname: Yu
authors.forename: Matko
authors.initials: M
authors.lastname: Čančer
authors.forename: Berith
authors.initials: B
authors.lastname: Nilsson
authors.forename: Justyna
authors.initials: J
authors.lastname: Leja
authors.forename: Magnus
authors.initials: M
authors.lastname: Essand
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000627:therapeutic use*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000235:genetics / Q000627:therapeutic use*; D004742:Enhancer Elements, Genetic; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000628:therapy*; D050504:Oncolytic Viruses / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: D017500:Adenovirus E1A Proteins; D051792:Basic Helix-Loop-Helix Proteins; D057846:Cell-Penetrating Peptides; C499317:Ascl1 protein, mouse
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