Abstract
Oncolytic viruses have demonstrated efficacy in numerous tumor models including non-small cell lung cancer (NSCLC). One limitation of viral therapy for metastatic lung cancer is that systemic administration can be hindered by complement and antiviral immunity. Thus, we investigated whether ex vivo-infected blood outgrowth endothelial cells (BOECs) could be used to deliver VSV-IFNβ in preclinical models of NSCLC. BOECs were obtained from human donors or C57/Bl6 mice. VSV was engineered to produce GFP or IFNβ. Human and murine BOECs could be infected by VSV-GFP and VSV-IFNβ. Infected BOECs resulted in killing of NSCLC cells in vitro and shielded VSV-IFNβ from antibody neutralization. Mouse BOECs localized to lungs of mice bearing syngeneic LM2 lung tumors, and infected murine BOECs reduced tumor burden in this model. In an immune-deficient A549 xenograft model, mice treated with VSV-IFNβ-infected human BOECs exhibited superior antitumor activity and survival of mice (n = 10, P < .05 compared to VSV-IFNβ alone). We conclude that BOECs can be used as a carrier for delivery of oncolytic VSV-IFNβ. This may be an effective strategy for clinical translation of oncolytic virotherapy for patients with metastatic NSCLC.
Original language | English (US) |
---|---|
Article number | 100782 |
Journal | Translational Oncology |
Volume | 13 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2020 |
Bibliographical note
Funding Information:This work was funded by grants from A Breath of Hope Lung Foundation and Minnesota Masonic Charities. The funding sources have had no role in the conduct of the research or in any aspect of the development of this manuscript.
Publisher Copyright:
© 2020 The Authors
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
Fingerprint
Dive into the research topics of 'Blood Outgrowth Endothelial Cells as a Cellular Carrier for Oncolytic Vesicular Stomatitis Virus Expressing Interferon-β in Preclinical Models of Non-Small Cell Lung Cancer'. Together they form a unique fingerprint.University Assets
-
-
University Imaging Centers
Mark A Sanders (Program Director) & Guillermo Marques (Scientific Director)
University Imaging CentersEquipment/facility: Facility