The Oncolytic Adenovirus VCN-01 as Therapeutic Approach Against Pediatric Osteosarcoma
| Autor: | Marisol Gonzalez-Huarriz, Enric Xipell, Marta M. Alonso, Arlet M. Acanda de la Rocha, Gemma Toledo, Marta Zalacain, Manel Cascallo, Naiara Martinez-Velez, Ramon Alemany, Beatriz Vera, Ana Patiño, Lucía Marrodán |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncolytic adenovirus Cancer Research Lung Neoplasms Mice Nude Bone Neoplasms Virus Replication medicine.disease_cause Pediatrics Adenoviridae Cell Line Mice 03 medical and health sciences 0302 clinical medicine In vivo Cell Line Tumor medicine Animals Humans Cytotoxicity Oncolytic Virotherapy Osteosarcoma business.industry Cancer Genetic Therapy medicine.disease Xenograft Model Antitumor Assays Oncolytic virus Oncolytic Viruses HEK293 Cells 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell Immunology Cancer research Female business |
| Zdroj: | Clinical Cancer Research. 22:2217-2225 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-15-1899 |
| Popis: | Purpose: 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. Experimental Design: 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. Results: 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. Conclusions: 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. |
| Databáze: | OpenAIRE |
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