Oncolytic Virotherapy for Multiple Myeloma Using Vesicular Stomatitis Virus

In this research project, Oncolytic Virotherapy for Multiple Myeloma Using Vesicular Stomatitis Virus, investigators with the Mayo Clinic Multiple Myeloma SPORE are working to develop a single-shot virotherapy cure for multiple myeloma.

Project researchers hope that through a two-stage process, a single dose of a newly developed oncolytic virus will destroy all multiple myeloma cells in the body.

This project builds on research from 2013, in which SPORE investigators administered a large dose of an oncolytic measles virus to a patient with multiply relapsed myeloma that was resistant to all available therapy. The patient had a dramatic response to the measles virus therapy and entered long-term remission.

However, it's unlikely that the measles virus therapy could be used in the majority of patients with multiple myeloma because these patients have anti-measles antibodies in their bloodstream. Because of this, Mayo Clinic researchers created a new oncolytic virus called VSV-IFNβ-NIS. This virus is derived from the vesicular stomatitis virus (VSV), which causes a blistering disease in cattle.

The IFNβ gene that has been inserted into the new virus makes it safer, more potent and more specific for myeloma therapy. The NIS gene allows researchers to image the location of virus-infected cells in a treated patient.

Oncolytic virus VSV-IFNβ-NIS is highly effective in mice with myeloma. Researchers believe it's also ideal for intravenous administration to patients with multiple myeloma because patients don't have antibodies to this virus.

This virotherapy project will advance the new oncolytic virus to phase I clinical testing in patients with treatment-resistant multiple myeloma. SPORE researchers hope this innovative bench-to-bedside strategy will ultimately result in a new treatment option for multiple myeloma.

This project addresses such crucial questions as:

  • What is the safety profile, toxicity and maximally tolerated dose of VSV-IFNβ-NIS?
  • What are the dynamics of virus spread using noninvasive imaging, viral persistence and antiviral immune response?
  • What are the factors associated with response to VSV-IFNβ-NIS therapy?

Anticipated outcomes of this research include:

  • Providing a new approach to the treatment of multiple myeloma
  • Exploiting novel imaging strategies to monitor the virus in vivo
  • Identifying myeloma antigens that robustly stimulate T cells in the context of oncolytic therapy
  • Optimizing vesicular stomatitis virus therapy by identifying key factors contributing to myeloma destruction and combination therapy approaches to enhance therapeutic response