GenVec Inc (fka GNVC)

[Teliz2009]

What is this new drug you’re studying?
Dr. Chang: This new treatment modality that we’re studying is very new, cutting edge and very exciting. It’s a new paradigm in cancer treatment. What it involves is a product called TNFerade, which is a tumor necrosis factor that is delivered by a virus into the cancer. The background of this is that our immune cells produce TNF, which is a cytokine protein that has anti-tumor properties. It kills cancer cells, but in small quantities. It’s produced in small quantities by our immune cells. So, the concept is that if we took the TNF and injected large quantities into the patient, the toxicity would be overwhelming. The challenge is to produce TNF inside the cancer cell and only in the cancer cells and not in the normal cells. What has been designed then for this therapy is to take the human TNF alpha gene and place that gene into a virus. The virus is also especially engineered not to replicate and cause viral illness. So, the virus is a vehicle to deliver the gene. That has been delivered to the tumor through yet another breakthrough in terms of a medical technology with endoscopic ultrasound. Endoscopic ultrasound is a scope that goes into the body, into the stomach, just like a routine endoscopy, but it allows us to see through the stomach into the tumor and we can then place a needle through the endoscope and deliver the virus directly into the tumor working from within the stomach and GI tract. Once we deliver the virus into the tumor, we deliver four times 10 to the ninth to four times 10 to the 11th viral particles. These viruses then spread among the cancer cells and attach to the cancer cells. Once it attaches, the TNF from the virus, the TNF gene from the virus is actually injected into the cancer cells and that’s what viruses do very well.
Once the TNF gene is injected into the cancer cell, the virus itself does not replicate and dies off. So, it’s done its kamikaze mission, and it’s delivered the TNF. When the TNF is in the cancer cell, it will start to replicate and produce TNF. The TNF will then destroy the cancer cell.
Now, this therapy also works in synergy with chemotherapy and radiation therapy, so it’s actually a combined synergistic modality. So, what happens is that the patient receives chemotherapy and this is the standard 5FU chemotherapy, which has anti-tumor effect as well as causes the tumor to be more radiation sensitive. Then the patient receives radiation, and the radiation has anti-tumor effect. The radiation also has a special effect on the TNF gene. It causes the TNF gene to replicate much faster, so it steps on the gas pedal. So now the TNF is being produced in larger quantities. The TNF has anti-tumor properties, and it also is a radiation sensitizer, so you can see that three different modalities, all synergistically, each one makes the other more potent and more powerful, so you have a really strong combination in this combined therapy.
So it is used in combination with these others, but for a reason? That’s designed very much that way.
Dr. Chang: That’s right. It’s designed in combination with chemotherapy and radiation therapy to active in synergy, as opposed to just an add-on, ABC, off-the-menu type thing.
Now how does the TNF that you’ve injected react after it’s worked on cancer? Does it die off eventually?
Dr. Chang: The TNF, the gene for TNF is in the cancer cell and the cancer cell itself will produce TNF. Then the TNF will destroy the cancer cell. There may be some spillover once the cancer cell is destroyed, but the half-life of TNF is rather short, and the chance of it spreading throughout the body is very small. During the trial, we measured the serum blood level of TNF, and it’s not detectable in most patients.
http://www.ivanhoe.com/channels/p_channelstory.cfm?storyid=7686