NSCs are permissive to oncolytic Myxoma virus and provide a delivery method for targeted ovarian cancer therapy.

NSCs are permissive to oncolytic Myxoma virus and provide a delivery method for targeted ovarian cancer therapy.
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神经干细胞对溶瘤粘液瘤病毒具有耐受性,并为靶向卵巢癌治疗提供了一种输送方法。

DOI:
10.18632/oncotarget.27845
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发表时间:
2020-12-22
期刊:
影响因子:
--
通讯作者:
Hammad M
Hammad M
中科院分区:
其他
文献类型:
--
作者:
Cornejo Y;Li M;Dellinger TH;Mooney R;Rahman MM;McFadden G;Aboody KS;Hammad M

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尽管在过去的20年中开发了许多抗癌药物,但卵巢癌仍然是最致命的妇科恶性肿瘤。由于缺乏有效的筛查,大多数卵巢癌患者在晚期被诊断出来,只有约20%的患者治愈。因此,除了改进的筛选方法之外,还迫切需要对晚期转移性疾病有效的新型抗癌剂。溶瘤病毒疗法是一种有前途的方法;不幸的是,将病毒全身递送至肿瘤仍然是一个重大挑战。在这方面,具有良好肿瘤归巢特性的神经干/祖细胞(NSC)可以作为溶瘤病毒的有效递送平台。在这项研究中,我们测试了粘液瘤病毒(MYXV)的疗效,这是一种兔特异性痘病毒,已被证明对各种肿瘤有效,使用人类和小鼠卵巢癌细胞系。我们发现MYXV在体外有效地裂解卵巢癌细胞,降低其活力。我们还证明了MYXV可以感染人NSC,特别是克隆HB1.F3.CD21 NSC系。总之,这些结果表明,神经干细胞介导的MYXV的交付可能是一个有前途的策略,实现更有选择性的靶向抗肿瘤疗效。
Despite the development of many anticancer agents over the past 20 years, ovarian cancer remains the most lethal gynecologic malignancy. Due to a lack of effective screening, the majority of patients with ovarian cancer are diagnosed at an advanced stage, and only ~20% of patients are cured. Thus, in addition to improved screening methods, there is an urgent need for novel anticancer agents that are effective against late-stage, metastatic disease. Oncolytic virotherapy is a promising approach; unfortunately, systemic delivery of viruses to tumors remains a major challenge. In this regard, neural stem/progenitor cells (NSCs) with well-established tumor-homing properties may serve as an effective delivery platform for oncolytic viruses. In this study, we tested the efficacy of myxoma virus (MYXV), a rabbit-specific poxvirus that has demonstrated efficacy against a variety of tumors, using human and mouse ovarian cancer cell lines. We showed that MYXV effectively lysed ovarian cancer cells in vitro, reducing their viability. We also demonstrated that MYXV can infect human NSCs, specifically the clonal HB1.F3.CD21 NSC line. Taken together, these results suggest that NSC-mediated delivery of MYXV may be a promising strategy for achieving more selectively targeted anti-tumor efficacy.