Department of Pediatric Hematology/Oncology, Phoenix Children's Hospital, Phoenix, Arizona 85016, USA.
Cancer. 2011 Apr 15;117(8):1764-74. doi: 10.1002/cncr.25741. Epub 2010 Nov 8.
Despite advancement in therapies, overall survival rates for relapsed pediatric sarcomas are dismal. Newer therapies are needed to effectively salvage these patients. Oncolytic viruses (such as reovirus) and other genetically altered viruses (such as herpes simplex viruses and adenoviruses) have shown efficacy in a variety of solid tumors including sarcomas. Reolysin is an unmodified oncolytic reovirus that selectively replicates in Ras-activated cancer cells while not causing any significant human illness in its wild form.
By using a panel of pediatric sarcoma cell lines in vitro and flank xenografts in vivo, Reolysin was evaluated as a single agent and in combination with cisplatin and radiation therapy. Electron microscopy and immunohistochemistry was used to demonstrated a cytopathic effect in treated tumors.
Reolysin inhibited the proliferation and viability of sarcoma cell lines at a dose of 1 to 10 virus particles per cell. In vivo, 5 × 10(9) plaque-forming units (PFU) administered via the tail vein every other day for 3 doses every 21 days inhibited the growth of tumor xenografts with improvement in event-free survival. In the SKES1 Ewing sarcoma line, there was therapeutic enhancement when reovirus was administered in combination with radiation or cisplatin. In the RH30 line and the OS33 line, therapeutic enhancement was demonstrated with radiation and cisplatin, respectively.
These results suggest that Reolysin alone or in combination with other cytotoxic agents may be effective therapy in pediatric sarcomas.
尽管治疗方法有所进步，但复发型儿科肉瘤的总体存活率仍然不容乐观。需要新的治疗方法来有效挽救这些患者。溶瘤病毒（如呼肠孤病毒）和其他经过基因改造的病毒（如单纯疱疹病毒和腺病毒）在多种实体肿瘤中（包括肉瘤）已显示出疗效。Reolysin 是一种未经修饰的溶瘤呼肠孤病毒，它可以选择性地在 Ras 激活的癌细胞中复制，而在其自然形式下不会引起任何显著的人类疾病。
通过在体外使用一系列儿科肉瘤细胞系和体内 flank 异种移植物，评估 Reolysin 作为单一药物以及与顺铂和放射治疗联合使用的效果。电子显微镜和免疫组织化学用于证明治疗肿瘤中的细胞病变效应。
Reolysin 以 1 至 10 个病毒颗粒/细胞的剂量抑制肉瘤细胞系的增殖和活力。在体内，通过尾静脉每两天给予 5×10(9) 噬菌斑形成单位（PFU），每 21 天给予 3 个剂量，可抑制肿瘤异种移植物的生长，改善无事件生存。在 SKES1 尤文肉瘤系中，当呼肠孤病毒与放射或顺铂联合使用时，有治疗增强作用。在 RH30 系和 OS33 系中，分别通过放射和顺铂显示出治疗增强作用。
这些结果表明，Reolysin 单独或与其他细胞毒性药物联合使用可能是儿科肉瘤的有效治疗方法。
