title: The Oncolytic Adenovirus VCN-01 as Therapeutic Approach Against Pediatric Osteosarcoma.
abstract: Osteosarcoma is the most common malignant bone tumor in children and adolescents. Despite aggressive chemotherapy, more than 30% of patients do not respond and develop bone or lung metastasis. Oncolytic adenoviruses engineered to specifically destroy cancer cells are a feasible option for osteosarcoma treatment. VCN-01 is a replication-competent adenovirus specifically engineered to replicate in tumors with a defective RB pathway, presents an enhanced infectivity through a modified fiber and an improved distribution through the expression of a soluble hyaluronidase. The aim of this study is to elucidate whether the use of VCN-01 would be an effective therapeutic strategy for pediatric osteosarcoma.
  
  
  
  We used osteosarcoma cell lines established from patients with metastatic disease (531MII, 678R, 588M, and 595M) and a commercial cell line (143B). MTT assays were carried out to evaluate the cytotoxicity of VCN-01. Hexon assays were used to evaluate the replication of the virus. Western blot analysis was performed to assess the expression levels of viral proteins and autophagic markers. The antitumor effect of VCN-01 was evaluated in orthotopic and metastatic osteosarcoma murine animal models.
  
  
  
  This study found that VCN-01, a new generation genetically modified oncolytic adenovirus, administered locally or systemically, had a potent antisarcoma effect in vitro and in vivo in mouse models of intratibial and lung metastatic osteosarcoma. Moreover, VCN-01 administration showed a safe toxicity profile.
  
  
  
  These results uncover VCN-01 as a promising strategy for osteosarcoma, setting the bases to propel a phase I/II trial for kids with this disease. Clin Cancer Res; 22(9); 2217-25. ©2015 AACR.
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain. Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain. Department of Medical Oncology, University Hospital of Navarra, Pamplona, Spain.
authors.forename: Naiara
authors.initials: N
authors.lastname: Martínez-Vélez
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain. Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain. Department of Medical Oncology, University Hospital of Navarra, Pamplona, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Xipell
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain. Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain. Department of Medical Oncology, University Hospital of Navarra, Pamplona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Vera
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain. Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain. Department of Medical Oncology, University Hospital of Navarra, Pamplona, Spain.
authors.forename: Arlet
authors.initials: A
authors.lastname: Acanda de la Rocha
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain. Department of Pediatrics, University Hospital of Navarra, Pamplona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Zalacain
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain. Department of Pediatrics, University Hospital of Navarra, Pamplona, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Marrodán
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain. Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain. Department of Medical Oncology, University Hospital of Navarra, Pamplona, Spain.
authors.forename: Marisol
authors.initials: M
authors.lastname: Gonzalez-Huarriz
authors.affiliation: Department of Pathology, MD Anderson Cancer Center, Madrid, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Toledo
authors.affiliation: VCN Biosciences, Sant Cugat del Vallés, Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Cascallo
authors.affiliation: Translational Research Laboratory, IDIBELL-Institut Catalá d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Alemany
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain. Department of Pediatrics, University Hospital of Navarra, Pamplona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Patiño
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain. Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain. Department of Medical Oncology, University Hospital of Navarra, Pamplona, Spain. mmalonso@unav.es.
authors.forename: Marta M
authors.initials: MM
authors.lastname: Alonso
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology / Q000821:virology*; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000821:virology; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics*; D012516:Osteosarcoma / Q000821:virology*; D010372:Pediatrics; D014779:Virus Replication / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods