Use of blood outgrowth endothelial cells as a carrier of oncolytic vesicular
stomatitis virus-interferon beta in treating metastatic non-small cell lung cancer
Yan Ji MD, PhD, Blake Jacobson PhD, Manish Patel, DO, Robert Kratzke MD
Division of Hematology/Oncology/Transplant, University of Minnesota, Minneapolis,
MN 55455
ABSTRACT
Oncolytic viruses have been extensively studies in the past two decades and are
promising for cancer treatment. Intratumoral injection of vesicular stomatitis virus (VSV)
viruses causes tumor shrinkage. However, systemic administration is required for
treating disseminated tumor. This approach has encountered a few challenges,
including low viral titer due to neutralization by serum factors as well as sequestration
in lymphoid tissue. In order to overcome these problems, different strategies have been
developed without much success. The current study is to explore the potential role of
blood outgrowth endothelial cells (BOECs) as carrier cells to deliver VSV-interferon
(IFN) to lung tumor sites. We demonstrated that VSV-IFNβ-infected BOECs can
effectively transfer VSV-IFNβ to co-cultured human lung cancer cells and caused cell
death. Moreover, BOECs protected VSV against its neutralizing antibody in vitro.
BOECs injected via tail vein preferentially accumulated in lung tumor tissues, and were
absent in either normal lung or liver tissues in our lung cancer mouse model. Based
on these findings, we expect BOECs will greatly enhance intratumoral viral titer and
result in greater antitumor activity. This hypothesis is supported by some of the
preliminary in vivo data. We plan to translate the findings from current into the clinical
settings, and develop a clinical protocol in the near future to assess the safety,
response and efficacy of VSV-IFNβ-infected BOECs in treatment of lung cancer.