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Ex Vivo Infection of Live Tissue with Oncolytic Viruses
12:08

Ex Vivo Infection of Live Tissue with Oncolytic Viruses

Published on: June 25, 2011

13.3K

Visualizing Oncolytic Virus-Host Interactions in Live Mice Using Intravital Microscopy

Victor Naumenko1,2,3,4, Shinia Van1,2,3, Himika Dastidar1,2,5

  • 1Alberta Children's Hospital Research Institute, Calgary, AB T2N 4N1, Canada.

Molecular Therapy Oncolytics
|August 4, 2018
PubMed

Insights

High-resolution 4D imaging of oncolytic virus (OV) interactions in live mice advances cancer therapy. This intravital microscopy technique visualizes virus delivery, tumor spread, and immune cell engagement, crucial for improving OV treatments.

Area of Science:

  • Oncolytic virotherapy
  • Cancer immunology
  • Microscopy and imaging

Background:

  • Oncolytic virus (OV) therapy shows promise for cancer treatment but has limited efficacy in most patients.
  • Improving OV therapy requires a deeper understanding of OV biology, including delivery, tumor microenvironment interactions, and immune modulation.
  • Current methods lack the resolution to visualize OV-host interactions in real-time within living organisms.

Purpose of the Study:

  • To establish and validate a high-resolution 4D imaging technique for studying OV-host interactions in vivo.
  • To visualize the dynamic processes of OV delivery, infection, and spread within the tumor microenvironment and host organs.
  • To provide a tool for better understanding the mechanisms underlying OV therapy efficacy and failure.

Main Methods:

  • Development of a 4D intravital microscopy (IVM) technique for live imaging in mice.
  • Labeling of oncolytic vesicular stomatitis virus (VSV) with Alexa Fluor dyes for visualization.
  • Utilizing fluorophore-tagged antibodies and reporter proteins to image target cells and viral infection.
  • Single- and multiphoton microscopy for high-resolution imaging of OV-host interactions in blood, tumors, and organs.

Main Results:

  • Demonstrated that Alexa Fluor-labeled VSV retains bioactivity in vivo and is readily visualized by IVM.
  • Successfully imaged dynamic interactions between VSV and host cells in real-time across various tissues.
  • Observed leukocyte binding and transport of VSV particles in blood.
  • Visualized VSV infection foci spreading within tumors.
  • Documented interactions between antigen-presenting cells and VSV in the spleen.

Conclusions:

  • Intravital microscopy provides unprecedented resolution for studying OV-host interactions in vivo.
  • This 4D imaging approach is a powerful new tool for advancing the development of oncolytic virus therapies.
  • Understanding these dynamic interactions is critical for optimizing OV delivery and enhancing anti-tumor immunity.
Keywords:
intravital microscopyoncolytic virussecondary lymphoid organstumor microenvironmentvirus-host interactions

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