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Influence of carrier cells on the clinical outcome of children with neuroblastoma treated with high dose of oncolytic adenovirus delivered in mesenchymal stem cells.

作者信息

Melen Gustavo J, Franco-Luzón Lidia, Ruano David, González-Murillo África, Alfranca Arantzazu, Casco Fernando, Lassaletta Álvaro, Alonso Mercedes, Madero Luís, Alemany Ramón, García-Castro Javier, Ramírez Manuel

机构信息

Fundación para la Investigación Biomédica, Hospital Universitario Niño Jesús, Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, Madrid, Spain.

Fundación Oncohematología Infantil, Madrid, Spain.

出版信息

Cancer Lett. 2016 Feb 28;371(2):161-70. doi: 10.1016/j.canlet.2015.11.036. Epub 2015 Dec 3.


DOI:10.1016/j.canlet.2015.11.036
PMID:26655276
Abstract

We report here our clinical experience of a program of compassionate use of Celyvir--autologous marrow-derived mesenchymal stem cells (MSCs) carrying an oncolytic adenovirus--for treating children with advanced metastatic neuroblastoma. Children received weekly doses of Celyvir with no concomitant treatments. The tolerance was excellent, with very mild and self-limited viral-related symptoms. Patients could be distinguished based on their response to therapy: those who had a clinical response (either complete, partial or stabilization) and those who did not respond. We found differences between patients who responded versus those who did not when analyzing their respective MSCs, at the expression levels of adhesion molecules (CCR1, CXCR1 and CXCR4) and in migration capacities in transwell assays, and in immune-related molecules (IFNγ, HLA-DR). These results suggest interpatient differences in the homing and immune modulation capacities of the therapy administered. In addition, the pretherapy immune T cell status and the T effector response were markedly different between responders and non-responders. We conclude that multidoses of Celyvir have an excellent safety profile in children with metastatic neuroblastoma. Intrinsic patients' and MSCs' factors appear to be related to clinical outcome.

摘要

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[4]
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