To enable IV delivery and tumor targeting of oncolytic viruses (OV) by decreasing virus clearance in circulation, Iscaro et al. encapsulated a prostate-specific oncolytic adenovirus (Ad[I/PPT-E1A]) into CCL2-coated liposomes (LP) that were taken up by CCR2-expressing circulating macrophages and delivered directly to hypoxic areas in the TME. LP encapsulation did not affect oncolytic activity in vitro or in vivo and did not cause toxicity. IV delivery of LP Ad[I/PPT-E1A] in a prostate tumor model resulted in a significant decrease in tumor size and lung metastases, requiring a 1000-fold lower dose of OV compared to Ad[I/PPT-E1A] alone.
Contributed by Katherine Turner
ABSTRACT: Oncolytic viruses (OV) selectively replicate in and destroy cancer cells resulting in anti-tumor immunity. However, clinical use remains a challenge because of virus clearance upon intravenous delivery. OV packaging using a nanomedicine approach could overcome this. Here we encapsulate an oncolytic adenovirus (Ad[I/PPT-E1A]) into CCL2-coated liposomes in order to exploit recruitment of CCR2-expressing circulating monocytes into tumors. We demonstrate successful encapsulation of Ad[I/PPT-E1A] into CCL2-coated liposomes that were preferentially taken up by CCR2-expressing monocytes. No complex-related toxicities were observed following incubation with prostate tumor cells and the encapsulation did not affect virus oncolytic activity in vitro. Furthermore, intravenous administration of our nanomedicine resulted in a significant reduction in tumor size and pulmonary metastasis in prostate cancer-bearing mice whereby a 1000-fold less virus was needed compared to Ad[I/PPT-E1A] alone. Taken together our data provides an opportunity to target OV via circulation to inaccessible tumors using liposome-assisted drug delivery.
Author Info: (1) Department of Oncology & Metabolism, University of Sheffield, Medical School, Beech Hill Road, Sheffield, S102RX, UK. (2) Department of Oncology & Metabolism, University of She
Author Info: (1) Department of Oncology & Metabolism, University of Sheffield, Medical School, Beech Hill Road, Sheffield, S102RX, UK. (2) Department of Oncology & Metabolism, University of Sheffield, Medical School, Beech Hill Road, Sheffield, S102RX, UK. (3) Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, Scotland. (4) Department of Oncology & Metabolism, University of Sheffield, Medical School, Beech Hill Road, Sheffield, S102RX, UK. (5) Department of Oncology & Metabolism, University of Sheffield, Medical School, Beech Hill Road, Sheffield, S102RX, UK. (6) Department of Oncology & Metabolism, University of Sheffield, Medical School, Beech Hill Road, Sheffield, S102RX, UK. (7) Department of Oncology & Metabolism, University of Sheffield, Medical School, Beech Hill Road, Sheffield, S102RX, UK. (8) Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, Scotland. (9) Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85, Uppsala, Sweden. (10) Department of Oncology & Metabolism, University of Sheffield, Medical School, Beech Hill Road, Sheffield, S102RX, UK. (11) Department of Radiology, Division Translational Nanobiomaterials and Imaging, Leiden University Medical Center, Leiden, the Netherlands. (12) Department of Oncology & Metabolism, University of Sheffield, Medical School, Beech Hill Road, Sheffield, S102RX, UK. (13) Department of Oncology & Metabolism, University of Sheffield, Medical School, Beech Hill Road, Sheffield, S102RX, UK. Electronic address: m.muthana@sheffield.ac.uk.
