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Treatment of metastatic neuroblastoma with systemic oncolytic virotherapy delivered by autologous mesenchymal stem cells: an exploratory study

Abstract

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.

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Acknowledgements

We thank Dr Samuel Navarro for help with electronic microscopy, Dr José Díaz for help with MIBG interpretation and Jaime Valentín for technical assistance. Financial support: JG-C supported by Grant FIS PI05/2217 (Instituto de Salud Carlos III) and TCRM 0027/2006 (Junta de Andalucía). MC supported by grant from Mutua Madrileña Medical Research Foundation. RA supported by EU 6th FP research contract 18700 (Theradpox, RA) and project Grant BIO2005-08682-C03-02/01 from the Spanish Ministry of Education and Science. RA belongs to the Network of Cooperative Research on Cancer (C03-10), Instituto de Salud Carlos III of the Ministerio de Sanidad y Consumo, Government of Spain.

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Correspondence to M Ramírez.

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García-Castro, J., Alemany, R., Cascalló, M. et al. Treatment of metastatic neuroblastoma with systemic oncolytic virotherapy delivered by autologous mesenchymal stem cells: an exploratory study. Cancer Gene Ther 17, 476–483 (2010). https://doi.org/10.1038/cgt.2010.4

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Keywords

  • mesenchymal stem cells
  • oncolytic adenoviruses
  • systemic delivery
  • neuroblastoma
  • metastases

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