TY - JOUR
T1 - NSCs are permissive to oncolytic Myxoma virus and provide a delivery method for targeted ovarian cancer therapy
AU - Cornejo, Yvonne
AU - Li, Min
AU - Dellinger, Thanh H.
AU - Mooney, Rachael
AU - Rahman, Masmudur M.
AU - McFadden, Grant
AU - Aboody, Karen S.
AU - Hammad, Mohamed
N1 - Funding Information:
This work was funded by STOP CANCER, the Rosalinde and Arthur Gilbert Foundation, the California Institute of Regenerative Medicine, the Alvarez Family Foundation, the Anthony F. & Susan M. Markel Foundation, the Ben and Catherine Ivy Foundation, City of Hope, and National Cancer Institute grants R43CA86768, R44CA8678, and R01CA197359. Research reported in this publication includes work performed by M.L. in the City of Hope Biostatistics Core, which is supported by the National Cancer Institute of the NIH under award number P30CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Materials Transfer Information is available from the City of Hope Office of Technology Licensing.
Publisher Copyright:
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.
PY - 2020/12/22
Y1 - 2020/12/22
N2 - 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.
AB - 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.
KW - Myxoma
KW - NSCs
KW - Oncolytic virotherapy
KW - Ovarian cancer
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U2 - 10.18632/ONCOTARGET.27845
DO - 10.18632/ONCOTARGET.27845
M3 - Article
C2 - 33473255
AN - SCOPUS:85099188846
SN - 1949-2553
VL - 11
SP - 4693
EP - 4698
JO - Oncotarget
JF - Oncotarget
IS - 51
ER -