title: 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.
authors.affiliation: Servicio de Oncohematología y Trasplante, Hospital Universitario Niño Jesús, Avenida Menéndez Pelayo 65, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: García-Castro
authors.forename: R
authors.initials: R
authors.lastname: Alemany
authors.forename: M
authors.initials: M
authors.lastname: Cascalló
authors.forename: J
authors.initials: J
authors.lastname: Martínez-Quintanilla
authors.forename: M del Mar
authors.initials: Mdel M
authors.lastname: Arriero
authors.forename: A
authors.initials: A
authors.lastname: Lassaletta
authors.forename: L
authors.initials: L
authors.lastname: Madero
authors.forename: M
authors.initials: M
authors.lastname: Ramírez
mesh_terms: D045744:Cell Line, Tumor; D002675:Child, Preschool; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000821:virology*; D009447:Neuroblastoma / Q000473:pathology / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000502:physiology