Intravital microscope tracks virus to kill cancer
Image: Intravital microscope [Pavel Melnikov, Pirogov Russian National Research Medical University]
For the first time ever, researchers have applied intravital microscopy to study the interaction of so-called oncolytic viruses with tumour cells and healthy cells.
Using the high-resolution 4D imaging method, Professor Douglas Mahoney from the University of Calgary, Canada, and colleagues, visualised how the virus behaves in the tissues of a living mouse.
"The method has a sufficient resolution to monitor the in vivo capture and transfer of viral particles by leukocytes, the spread of the infection site in tumours, and the activation of immune processes in the spleen and lymph nodes," highlights Mahoney's colleague, Victor Naumenko from the National University of Science and Technology, Russia. "We believe that this technology is a powerful new tool for studying and optimising virotherapy."
Oncolytic virus therapy is an emerging cancer treatment that uses replicating viruses to infect and kill tumour cells as well as triggering anti-cancer immunity.
But while the approach shows promise, it currently fails most patients.
To better understand processes relating to the therapy, Mahoney and colleagues established a technique for high-resolution 4D imaging of oncolytic virus-host interactions within intact tissues of live mice using intravital microscopy.
By labelling the the oncolytic vesicular stomatitis virus with Alexa Fluor dyes, they could easily study dynamics using single- or multiphoton microscopy while retaining bioactivity in vivo.
As the researchers explain in Molecular Therapy Oncolytics, the addition of fluorophore-tagged antibodies and genetically encoded reporter proteins to target cells and the virus, enabled real-time imaging of dynamic interactions between the virus and host cells in blood, tumour, and visceral organs of live mice.
"We conducted our experiments on the vesicular stomatitis virus, which is completely safe for humans, easy to genetically modify and easy to produce in large quantities," explains Mahoney's colleague, Victor Naumenko. "The virus can be marked with dyes that preserve its biological activity and provide visualisation in animal tissues through single- and two-photon microscopy."
The researchers reckon the straightforward method could easily be adopted by other laboratories.
"Future studies using intravital-microscopy should aid in the interrogation of Oncolytic virus biology and the subsequent development of more effective Oncolytic virus strains, dosing regimens, and combination therapies," says Naumenko.
Research is published in Molecular Therapy Oncolytics.