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神经干细胞对溶瘤作用具有易感性,并为靶向性卵巢癌治疗提供了一种递送方法。

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

作者信息

Cornejo Yvonne, Li Min, Dellinger Thanh H, Mooney Rachael, Rahman Masmudur M, McFadden Grant, Aboody Karen S, Hammad Mohamed

机构信息

Department of Stem Cell & Developmental Biology, City of Hope, Duarte, CA 91010, USA.

Irell & Manella Graduate School for Biological Sciences, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.

出版信息

Oncotarget. 2020 Dec 22;11(51):4693-4698. doi: 10.18632/oncotarget.27845.

DOI:10.18632/oncotarget.27845
PMID:33473255
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7771716/
Abstract

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 (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 , 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.

摘要

尽管在过去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方法,大多数卵巢癌患者在晚期才被诊断出来,只有约20%的患者能被治愈。因此,除了改进筛查方法外,迫切需要对晚期转移性疾病有效的新型抗癌药物。溶瘤病毒疗法是一种很有前景的方法;不幸的是,将病毒全身性递送至肿瘤仍然是一个重大挑战。在这方面,具有成熟肿瘤归巢特性的神经干/祖细胞(NSC)可能作为溶瘤病毒的有效递送平台。在本研究中,我们使用人和小鼠卵巢癌细胞系测试了兔特异性痘病毒黏液瘤病毒(MYXV)的疗效,该病毒已证明对多种肿瘤有效。我们发现MYXV能有效裂解卵巢癌细胞,降低其活力。我们还证明MYXV能感染人NSC,特别是克隆性HB1.F3.CD21 NSC系。综上所述,这些结果表明NSC介导的MYXV递送可能是实现更具选择性靶向抗肿瘤疗效的一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/615b/7771716/51a27b3d0457/oncotarget-11-4693-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/615b/7771716/f9ed6e03a7a8/oncotarget-11-4693-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/615b/7771716/51a27b3d0457/oncotarget-11-4693-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/615b/7771716/f9ed6e03a7a8/oncotarget-11-4693-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/615b/7771716/51a27b3d0457/oncotarget-11-4693-g002.jpg

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Oncolytic Viruses for Cancer Therapy: Barriers and Recent Advances.用于癌症治疗的溶瘤病毒:障碍与最新进展
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Development of Allogeneic Stem Cell-Based Platform for Delivery and Potentiation of Oncolytic Virotherapy.基于异基因干细胞的溶瘤病毒疗法递送与增效平台的开发。
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