Servicio de Oncohematología y Trasplante, Hospital Universitario Niño Jesús, Avenida Menéndez Pelayo 65, Madrid, Spain.
Cancer Gene Ther. 2010 Jul;17(7):476-83. doi: 10.1038/cgt.2010.4. Epub 2010 Feb 19.
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.
利用选择性复制肿瘤细胞的工程化腺病毒治疗转移性肿瘤是癌症治疗的一种新方法。全身给予这些溶瘤腺病毒缺乏转移性靶向能力。静脉内注射的间充质干细胞 (MSCs) 的肿瘤基质植入特性可能允许将 MSCs 用作靶向递送的细胞载体。在这项工作中，我们研究了输注自体感染 ICOVIR-5 的 MSC 的安全性和有效性，ICOVIR-5 是一种新型溶瘤腺病毒，用于治疗转移性神经母细胞瘤。根据一项批准的初步研究，4 名对一线治疗耐药的转移性神经母细胞瘤患儿接受了几次携带 ICOVIR-5 的自体 MSC 治疗。治疗的耐受性非常好。在一个病例中记录了完全临床缓解，并且该患儿在该治疗后 3 年完全缓解。我们假设 MSC 可以将溶瘤腺病毒递送至转移性肿瘤，而全身毒性非常低，并具有有益的抗肿瘤作用。
