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

2020; Impact Journals LLC; Volume: 11; Issue: 51 Linguagem: Inglês

10.18632/oncotarget.27845

1949-2553

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

Viral-associated cancers and disorders

// Yvonne Cornejo 1 , 2 , Min Li 3 , Thanh H. Dellinger 4 , Rachael Mooney 1 , Masmudur M. Rahman 5 , Grant McFadden 5 , Karen S. Aboody 1 , 6 and Mohamed Hammad 1 1 Department of Stem Cell & Developmental Biology, City of Hope, Duarte, CA 91010, USA 2 Irell & Manella Graduate School for Biological Sciences, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA 3 Department of Information Sciences, Division of Biostatistics at the Beckman Research Institute, City of Hope, Duarte, CA 91010, USA 4 Division of Gynecologic Surgery, Department of Surgery, City of Hope, CA 91010, USA 5 Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA 6 Division of Neurosurgery, City of Hope, Duarte, CA 91010, USA Correspondence to: Mohamed Hammad, email: mhammad@coh.org Keywords: oncolytic virotherapy; myxoma; NSCs; ovarian cancer Received: October 09, 2020 Accepted: December 03, 2020 Published: December 22, 2020 Copyright: © 2020 Cornejo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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 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.