Duke researchers engineer polio virus for cancer treatment

A new experimental cancer therapy involving a re-engineered polio virus is undergoing clinical trials here at Duke. After more than 20 years of development, the researchers and physicians of the Preston Robert Tisch Brain Tumor Center are now in the first phase of testing the polio virus in patients with glioblastomas, one of the deadliest and most aggressive types of brain cancer. Their promising results were recently featured in two 60 Minutes segments, which detailed the stories of the trial’s 22 patients. Neuro-oncologist Dr. Annick Desjardins is one of the main physicians of the study, and The Chronicle’s Abigail Xie spoke with Desjardins about what this new study might mean—and what it might not.

The Chronicle: Can you give some background of the study? How did it come about, what was the reasoning behind using polio to treat cancer?

Annick Desjardins: The idea of using viruses for cancer has been there for over a hundred years, and it’s always been very interesting but no one had the technology to do it or knew how. Dr. Mattias Gromeier figured out that polio virus has this ability to attach to any solid tumor cancer cell—lung, breast, brain, prostate. The problem is that polio can also attach to neurons which is how people develop the polio disease. So he removed the toxic part that infected normal neurons, replaced it with the cold virus and kept only the part that attached to cancer cells. That’s why the modified virus is benign, but when we inject the modified polio virus directly into the tumor, it will infect a few of the cancer cells. The polio virus dies very rapidly, but it wakes up the immune system, making the immune system think polio is around and attacking the cancer cells.

TC: You mentioned that the idea of using viruses to kill cancer is not a new one—so what has finally allowed an approach like this to advance into clinical trials?

AD: There are a lot of other viruses being tested. The thing is, with most of the other viruses, you just hope they will infect the cancer cells. What makes this one different is that it’s specific—you know it will attach to the cancer cells. Why it took so long, and the reason we had to do so many studies over 25 years is because it’s polio. People were scared. We had to do a lot of studies on animals. It was years of just safety studies, in order to prove we won’t give polio to the patient, and also to prove we won’t trigger an epidemic in the population.

TC: So far, of the 22 patients that have undergone this therapy, 11 have died and 2 have been declared cancer-free. Most people would see this number and focus on the deaths that have happened. But did the treatment overall prolong life by significant amount?

AD: Our trials are for patients with glioblastoma that has returned after treatment or surgery, so the fact that we have patients living now—three years after they were treated with the new therapy, three years since they’ve had a recurrence—it’s pretty amazing. We have patients that remain alive longer than the nine months we would have expected. But at this stage of clinical trials, the goal isn’t to look for the survival of the patient, because we’re really looking at the safety. The two patients that have done really well are encouraging for the others, and pushing us to find the right dose [of virus].

TC: What do you mean by focusing on the “safety” of the patient?

AD: So our trials are in Phase One, which means you’re looking at what the right dose of the drug is and how the patients tolerate it. For example, with chemotherapy, you want to increase the dose of chemo as much as you can and as much as the patient can tolerate. You always have to find this fine balance, right below the level that’s too toxic. You’re finding what’s the maximum dose I can give without giving my patient a drop in blood counts, risk of infection, nausea. What we’ve learned is that the virus works like the opposite of chemo - less is better. There are side effects like inflammation when you wake up the immune system, so that’s what we’re adjusting right now—how much of the virus can we give so it’s enough to kill the tumor but not so much the patient can’t tolerate. We’re not supposed to talk about survival in Phase One, but what’s cool is that we actually are seeing survival.

TC: Every so often, you hear in the news about some potential “cure” for cancer or some miracle that scientists have worked out. How close are we really to “curing” cancer? And is there any danger in the media covering a study like this, in misinformed patients thinking there’s a miracle cure?

AD: We don’t talk about a cure in cancer, we talk about remission. The goal of cancer is to grow and divide, and we never really know what the cancer cells will decide to do in order to keep growing. Like with too much antibiotics, bacteria learn to become resistant. Same thing with cancer—it builds up ways to fight what we’re doing. What we hope is that it will be harder to fight immunotherapy, but we have to be really smart and not think we have a cure. We just have to be alert for what it might throw at us next.