A new class of compounds is generating excitement for its ability to enhance the efficacy of oncolytic viruses (OVs) and to stimulate the immune response against tumours when used in combination therapy.
A recent paper published in Molecular Therapy by the TFRI-funded Canadian Oncolytic Virus Consortium (COVCo) has shown the ability of vanadium compounds (immuno-modulating, small molecule protein tyrosine phosphatase inhibitors) to improve the efficacy of OVs in cancer treatment. OV therapy – using viruses to stimulate a patient’s own immune system to kill cancer without damaging normal cells – can be very effective, yet some patients don’t respond to OVs alone.
The present study, led by Dr. Jean-Simon Diallo (Ottawa Hospital Research Institute), showed that combining vanadium compounds with OVs maximized viral oncolysis and systemic anticancer immunity. Importantly, this was true even in cases where the models were refractory to the drug and the OV alone – a finding that could potentially bring hope to patients who face similar challenges.
Further, the vanadium compounds were able to reverse a signal that would normally lead the tumour to raise its defenses against the virus into one that alarms the immune system towards the presence of the tumour. This occurred when the vanadate inhibited the Type I interferon response and potentiated a pro-inflammatory response via Type II interferon. Notably, the study showed that vanadate preferentially increased the growth of the virus in tumour cores with no impact on normal tissues.
While no other groups have explored vanadium in combination with oncolytic viruses, the compound has been previously used in clinical trials as an anti-diabetic medication. While it was found to be safe, it did not elicit the desired effect for diabetes treatment and was dropped. The COVCo group is now benefitting from the existing knowledge of vanadium, and hopes to soon bring their groundbreaking pre-clinical findings into clinical trials to continue the development of improved immunotherapy treatments for cancer.
Study: Multi-modal Potentiation of Oncolytic Virotherapy by Vanadium Compounds
Authors: Mohammed Selman, Christopher Rousso, Anabel Bergeron, Hwan Hee Son, Ramya Krishnan, Nader A. El-Sayes, Oliver Varette, Andrew Chen, Fabrice Le Boeuf, Fanny Tzelepis, John C. Bell, Debbie C. Crans, and Jean-Simon Diallo.
Funding: This paper was supported in part by grants to J.S.D. and J.C.B. from the Terry Fox Research Institute.