Journal
CANCER GENE THERAPY
Volume 17, Issue 7, Pages 476-483Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cgt.2010.4
Keywords
mesenchymal stem cells; oncolytic adenoviruses; systemic delivery; neuroblastoma; metastases
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Funding
- Instituto de Salud Carlos III [FIS PI05/2217]
- Junta de Andalucia [TCRM 0027/2006]
- Mutua Madrilena Medical Research Foundation
- EU (Theradpox, RA) [18700]
- Spanish Ministry of Education and Science [BIO2005-08682-C03-02/01]
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Treatment of metastatic tumors with engineered adenoviruses that replicate selectively in tumor cells is a new therapeutic approach in cancer. Systemic administration of these oncolytic adenoviruses lack metastatic targeting ability. The tumor stroma engrafting property of intravenously injected mesenchymal stem cells (MSCs) may allow the use of MSCs as cellular vehicles for targeted delivery. In this work, we study the safety and the efficacy of infusing autologous MSCs infected with ICOVIR-5, a new oncolytic adenovirus, for treating metastatic neuroblastoma. Four children with metastatic neuroblastoma refractory to front-line therapies received several doses of autologous MSCs carrying ICOVIR-5, under an approved preliminary study. The tolerance to the treatment was excellent. A complete clinical response was documented in one case, and the child is in complete remission 3 years after this therapy. We postulate that MSCs can deliver oncolytic adenoviruses to metastatic tumors with very low systemic toxicity and with beneficial antitumor effects. Cancer Gene Therapy (2010) 17, 476-483; doi:10.1038/cgt.2010.4; published online 19 February 2010
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