The Vacciniavirus construct GLV-1h153, engineered to encode for the human sodium iodide symporter gene (hNIS), is a promising candidate for virotherapy of cancer and for long-term noninvasive monitoring of therapeutic response via deep tissue imaging modalities such as positron emission tomography (PET).

This virus construct can also be used for targeted radiotherapy, according to study results presented at the Second AACR International Conference on Frontiers in Basic Cancer Research, held September 14-18, 2011, in San Francisco (CA, USA).

Dana Haddad, MD, PhD, who at the time of the study was a postdoctoral research fellow at Memorial Sloan-Kettering Cancer Center (New York, NY, USA) and is now a resident at the Mayo Clinic (Scottsdale, AZ, US), reported that GLV-1h153-treated pancreatic tumors from more than 50 mice were treated and imaged to provide insight into tumor therapeutic response.

The combination of GLV-1h153 and radioiodine (¹³¹I) was promising for targeted radiotherapy and destruction of pancreatic tumors. “We expected that we would be able to noninvasively detect virus replication in tumors using this imaging system, but we could not predict the timing of this, how long we could repeat serial imaging and whether this would actually provide information about therapeutic response,” said Dr. Haddad.

The researchers, who also included scientists from Genelux Corp. (San Diego, CA, USA), were initially discouraged when the PET signal in pancreatic tumors began to fade about two weeks after treatment with the virus, according to Dr. Haddad. However, she said they investigated what could be the cause of this loss of signal and were “pleased to ascertain that it was likely due to tumor kill and necrosis.”

The investigators found that hNIS-mediated radio-uptake noninvasively imaged with PET initially provided information into the presence of viral replication in the tumor, and later provided insight into the therapeutic response and biologic activity of cancer cells. “When the tumor began to die due to the effects of the virus, the PET signal began to decrease,” noted Dr. Haddad. “We were further pleased to observe that although tumor kill with a very low dose of virus was not very impressive, we could achieve potent tumor kill when we combined virus treatment with systemic radiotherapy. Using lower doses of virus and radiotherapy could minimize potential toxicity and side effects associated with both treatments.”

Additional research of viral and radiotracer dosing, and their effects on therapeutic response and imaging potential is currently being planned, according to Dr. Haddad.

Related Links:
Memorial Sloan-Kettering Cancer Center
Genelux