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September 10, 2018

Interaction of Oncolytic Viruses Observed with Both Tumor and Healthy Cells

Intravital microscope [© Pavel Melnikov, Pirogov Russian National Research Medical University]

  • Researchers from the Russia-based National University of Science and Technology (NUST) MISIS and the University of Calgary say they have learned how to observe the processes of oncolytic viruses in cancer cells in real time. For the first time, the intravital microscopy method was used to study the interaction of oncolytic viruses with both tumor and healthy cells, according to the scientists.

    The study (“Visualizing Oncolytic Virus-Host Interactions in Live Mice Using Intravital Microscopy”) appears in Molecular Therapy Oncolytics.

     

  • The arrows indicate examples of white blood cells connected with many viral particles, forming a «halo» around the cell surface.[© NUST MISIS]
  • Physicians typically treat cancer surgically, or through either radiation or chemotherapy. Therapy with an oncolytic virus (virotherapy or oncolytics) is a fairly new and promising technique for cancer treatment based on the creation (including the methods to genetically engineer them) of modified viruses that target and kill tumor cells. 

    Oncolytic viruses also stimulate anticancer immunity, which leads the tumor to destroy itself. The mechanism is as follows: the cancer cell, affected by the virus, releases signals to the immune system which cause it to recognize the tumor and to direct T-killer cells to fight it. 

    Although this method is being studied in the U.S., Europe, and China, and is considered promising, it hasn't yet received mass application. This is largely due to a lack of understanding how these oncolytic viruses work, notes the research team.

  • Microscopy of monocytes, capturing the virus (in blue) in tumor vessels. The arrow points to several localized virus particles on the cell surface.[© NUST MISIS]
  • Victor Naumenko, a candidate of medical sciences and a researcher at the NUST MISIS Biomedical Nanomaterials Laboratory, has applied advanced intravital microscopy to study the delivery of the virus to a tumor to monitor the dynamics of the virus’s spread and to stimulate the immune system.

    “While [oncolytic virus (OV) therapy] shows promise, it currently fails most patients, indicating strategies to improve OV activity are needed. Developing these will require a greater understanding of OV biology, particularly in the context of OV delivery and clearance, the infection process within a complex tumor microenvironment, and the modulation of anticancer immunity. To help achieve this, we have established a technique for high-resolution 4D imaging of OV-host interactions within intact tissues of live mice using intravital microscopy (IVM),” write the investigators.

    “We show that oncolytic vesicular stomatitis virus (VSV) directly labeled with Alexa Fluor dyes is easily visualized by single- or multiphoton microscopy while retaining bioactivity in vivo. The addition of fluorophore-tagged antibodies and genetically encoded reporter proteins to image target cells and the virus infection enables real-time imaging of dynamic interactions between VSV and host cells in blood, tumor, and visceral organs of live mice. The method has sufficient in vivo resolution to observe leukocytes in blood binding to and transporting VSV particles, foci of VSV infection spreading through a tumor, and antigen-presenting cells in the spleen interacting with and being infected by VSV. Visualizing OV-host interactions by IVM represents a powerful new tool for studying OV therapy.”

     

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