Journal
ONCOTARGET
Volume 6, Issue 33, Pages 34774-34787Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.5793
Keywords
oncolytic herpes simplex virus; viral retargeting; mesenchymal stem cells; systemic delivery; metastases
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Funding
- ERC ADG [340060]
- Italian Association for cancer research (AIRC) [IG14535, IG15324]
- University of Bologna FARB Project [RFBO121825]
- Ministry of Education, University and Research (MIUR)
- Department through the Pallotti legacy
- European Research Council (ERC) [340060] Funding Source: European Research Council (ERC)
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Fully retargeted oncolytic herpes simplex viruses (o-HSVs) gain cancer-specificity from redirection of tropism to cancer-specific receptors, and are non-attenuated. To overcome the hurdles of systemic delivery, and enable oncolytic viruses (o-viruses) to reach metastatic sites, carrier cells are being exploited. Mesenchymal stromal cells (MSCs) were never tested as carriers of retargeted o-viruses, given their scarse-null expression of the cancer-specific receptors. We report that MSCs from different sources can be forcedly infected with a HER2-retargeted oncolytic HSV. Progeny virus spread from MSCs to cancer cells in vitro and in vivo. We evaluated the organ distribution and therapeutic efficacy in two murine models of metastatic cancers, following a single i.v. injection of infected MSCs. As expected, the highest concentration of carrier-cells and of viral genomes was in the lungs. Viral genomes persisted throughout the body for at least two days. The growth of ovarian cancer lung metastases in nude mice was strongly inhibited, and the majority of treated mice appeared metastasis-free. The treatment significantly inhibited also breast cancer metastases to the brain in NSG mice, and reduced by more than one-half the metastatic burden in the brain.
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