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.
Highlights
Chemotherapy and surgery have improved greatly over the last several years, ovarian cancer remains lethal with over 21,000 women in the United States expected to be newly diagnosed and almost 14,000 deaths expected this year alone [1,2,3]
We incubated human (OVCAR8 and SKOV3) and murine (ID8) ovarian cancer cells with myxoma virus (MYXV) expressing fluorescence reporter proteins GFP and TdTr. These ovarian cancer cells were infected at a multiplicity of infection (MOI) of 10 and time-lapse images captured every 8 h for 48 h post-infection
We observed that all cell lines infected with vMyx-GFP-TdTr at MOIs of 3–10 have shown reduced viability compared to noninfected ones (Figure 1G–1I)
Summary
Chemotherapy and surgery have improved greatly over the last several years, ovarian cancer remains lethal with over 21,000 women in the United States expected to be newly diagnosed and almost 14,000 deaths expected this year alone [1,2,3]. One of the major limitations to effectively treating ovarian cancer is that most patients are diagnosed only after their primary tumor metastasizes to the abdomen and by that time their five-year survival rate is about 45% after Standard Of Care (SOC) treatment [4]. One promising strategy is the use of oncolytic viruses (OVs). These viruses take advantage of faulty mechanisms or pathways commonly found in tumor cells, which allows them to infect and replicate within the tumor cells while sparing healthy cells [5, 6]. Since new tumor antigens are exposed upon lysis, OVs are able to stimulate immune recognition of the cancer cells, further enhancing their therapeutic efficacy [8, 9]
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