Enhanced Combinatorial Oncolytic Virotherapy

Oncolytic viruses (OVs) are able to selectively infect and kill cancer cells without damaging normal cells. They can be used as a monotherapy, or they can be combined with existing cancer therapeutics for increased potency. While much progress has been made around OVs, one of their biggest limitations is their inability to successfully replicate, spread, and kill cancer cells in a complex tumor microenvironment.

 

Myxoma virus (MYXV) is one such OV which has garnered significant interest, particularly because it infects only rabbits in nature and does not cause harm in humans. However, MYXV can and does selectively infect and kill cancer cells that originate from human, mouse and other host species.

 

Prof. Masmudur Rahman, at the Biodesign Institute of Arizona State University has developed an enhanced oncolytic virotherapy regimen which combines a nuclear export inhibitor and an effective amount of recombinant MYXVs for treating cancer. This combination significantly enhances MYXV replication in 2D and 3D cell cultures as well as in human xenograft tumor models in NSG mice. This drug plus MYXV combination significantly enhanced cancer cell death at a low multiplicity of infection and a lower concentration of drug. When tested in xenograft tumor models, the combination of nuclear export inhibitor and MYXV reduced tumor burden and increased the survival of mice.

 

This positively demonstrates that OV-mediated activation of cell death pathways can synergistically function with nuclear export inhibitors as a potential new anti-cancer combinatorial therapy.

 

Potential Applications

Benefits and Advantages

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