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S. Russell
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-110 - Use of Blood Outgrowth Endothelial Cells as a Carrier of Oncolytic Vesicular Stomatitis Virus-Interferon Beta in Treating Metastatic NSCLC (ID 1008)
09:30 - 09:30 | Author(s): S. Russell
- Abstract
Background:
Oncolytic viruses have been extensively studies in the past two decades and are promising for cancer treatment. We have shown previously that vesicular stomatitis virus expressing interferon β (VSV-IFNβ) has oncolytic activity in vitro and in vivo in an immune competent mouse model of NSCLC. However, for treatment of metastatic NSCLC, intravenous delivery of VSV-IFNβ still faces several challenges, such as rapid clearance from bloodstream due to serum complement as well as sequestration in lymphoid tissue. In order to overcome these problems, we are exploring the potential role of blood outgrowth endothelial cells (BOECs) as carrier cells to deliver VSV-IFNβ to lung tumor sites.
Methods:
Efficacy of VSV-IFNβ-infected BOECs in transferring VSV-IFNβ to co-cultured human lung cancer cell lines in presence or absence of VSV antiserum were tested in vitro. A/J mice intravenously injected with LM2 non-small cell lung cancer cells were treated with PBS, VSV-IFNβ or VSV-IFNβ-infected BOECs (3 sequential treatments 3 weeks after tumor cell injection). Tumor growth, intratumor viral titer and survival were tested.
Results:
We demonstrated that VSV-IFNβ-infected BOECs can effectively transfer VSV-IFNβ to co-cultured human lung cancer cells and result in viral oncolysis even in the presence of VSV antiserum. In mice bearing metastatic lung cancer, BOECs injected via tail vein preferentially accumulated in lung tumor tissues, and were absent in either normal lung or liver tissues. Moreover, treatment with VSV-IFNβ-BOECs had higher and more sustained intra-tumoral viral titers comparing with those treated with either PBS or naked VSV-IFNβ. Furthermore, there was a trend (p=0.09) towards reduced tumor burden in the VSV-IFNβ-BOEC treated mice (n=5). Currently, we are testing the survival benefit of VSV virus in metastatic lung cancer model.
Conclusion:
In summary, the pre-clinical data showed promise to support developing a clinical protocol in the near future to assess the safety, response and efficacy of VSV-IFNβ-infected BOECs in treatment of metastatic lung cancer.
