Tamarah Westmoreland, MD, PhD, Pediatric Surgeon at Nemours Children’s Hospital talks about utilizing the zika virus to treat neruoblastoma.
How did the idea of using Zika to treat cancer come about?
WESTMORELAND: My specialty is pediatric cancer research, and one of my colleagues, Dr. Ken Alexander, is a virologist. He had been studying and reading papers about Zika virus and found a paper where they used a neuroblastoma cell line just to study Zika virus. They were not studying the effects of Zika on neuroblastoma, yet they reported in their paper that Zika virus killed their cell line. So, Dr. Alexander came to me and also contacted Dr. Griff Parks at UCF, who is a virologist. We came together to develop the project to see if Zika virus could be used to treat neuroblastoma.
Talk to me a little bit about the science. How does using a virus like Zika kill the cancer or work to reduce the cancer?
WESTMORELAND: The Zika virus attaches to a protein that’s on the cell wall of cancer. What’s interesting is we have identified that protein and it’s called CD24. It is unique to the cancer, so you don’t normally have this cell wall protein in your normal cells. The Zika virus attaches to this, which allows entry of the virus into the cell to kill the cell.
Are there some neuroblastoma tumors that don’t have the CD24 protein that wouldn’t necessarily work for?
WESTMORELAND: Neuroblastoma is a large spectrum. It ranges from tumors that spontaneously regress or go away on their own with no treatment. Those are normally in your infants. Then, it can continue all the way to a benign form of ganglia neuroblastoma. Within this wide range, you can have very aggressive neuroblastoma, or stage 4 or high-risk neuroblastoma, and their survival is only about 40%, even with advanced treatment. So, all the tumors that we primarily focus on are the high-risk neuroblastoma because the survival is so poor. All of those that we have tested do have the protein CD24 on their surface.
With the clinical trials or studies that you have looked into, what findings have you found so far?
WESTMORELAND: Well, we haven’t done clinical trials just yet. We are in mice and translating it to mice. What we have found is that approximately 90% of the neuroblastoma is killed with a single injection of Zika virus. This is neuroblastoma that we’ve grown on the side of a mouse that does not have a normal immune system, so that it allows the tumor to grow. These are excellent results in neuroblastoma, and we’ve extended them to some other pediatric tumors as well.
How long did it take to kill off the tumor?
WESTMORELAND: It takes about eight weeks for the tumor to grow big enough in the mice. Then we harvest the tumor about two weeks after the injection.
So, it takes about two weeks after the injection for the tumor to be killed off?
WESTMORELAND: Yes. I haven’t looked at a week or a week and a half yet. Those are other things that we’ll fine tune. But right now, we’re looking at two weeks and see 90% cell death. What’s interesting is, when you’re looking at the slides, you can see that the virus is moving across the tumor, killing the tumor. One thing that we’ve talked about doing in the future is waiting even a little longer. Maybe we are cutting the virus off too soon at two weeks and need a little longer, like three weeks.
What do you plan to do with these findings?
WESTMORELAND: In that experiment, we injected Zika virus just one time. We have an experiment that we are getting ready to start where we have the high-risk neuroblastoma cells growing on the immuno-deficient mice, and we’re going to give different doses of Zika virus at different intervals because the 90% percent was at a one-time dose. How much can we get if we, in those two-week periods, did two doses? So, we’re looking at different dosages right now.
What do you believe this will mean for someone’s parents or their child itself that has cancer? What do you think this will mean for their quality of life?
WESTMORELAND: We’re still early in translating this to humans. But if you look at treatment for cancers and many other things, they started in a basic science lab, and that’s what we are. We consider ourselves translational scientists because we’re translating what we see in a little petri dish to mice, and then hopefully, to either higher primate monkey and then human. What I would say to families is, this should give you hope. It is not that there are not people out there looking for better ways to treat devastating pediatric tumors.
Do you believe you’ll find any roadblocks or limitations when you finally get to that point of starting clinical trials with children?
WESTMORELAND: I think that we will potentially because Zika virus, when you hear that, it gives people fear. But I think as we educate more and learn even more about the virus, as well as perform the trials in mice and potentially higher primates, I think that we will show its safety profile and potential for treatment.
How do you administer it?
WESTMORELAND: Right now, we administer the Zika virus by injection. We inject it directly into the tumor. But that is another question that we will be looking at, is intravenous injection versus direct tumor injection. We have thought about, once the tumor is surgically removed, injecting the bed where the tumor was with Zika virus because one of the problems with tumors is when they come back. When they come back, sometimes they are resistant to the chemotherapy or radiation therapy that has been used to treat them. So at the time of surgery, we know that even though the margins are negative, the cells around the tumor do have some level of transformation. So, injecting Zika virus into the bed of where the tumor was is a potential opportunity.
Have you noticed any unexpected side effects?
WESTMORELAND: So far, we have not noticed any side effects from delivering Zika virus. We have studied delivering Zika virus alone to mice with no tumors and followed them out many weeks looking for any side effects. Now, Zika virus does not normally grow in mice. But we needed to make sure that, as a model, when we see death of a tumor, it is not because there is a problem with a mouse, per se.
Is there anything I didn’t ask you that you feel people should know?
WESTMORELAND: I think people need to realize, right here in central Florida, that there is excellent research going on and that we do this for the families. Both Dr. Alexander and I are clinicians. So, we take care of these patients. I operate on these patients, these children, and it means a great deal to both of us when we find improvements or ideas to try to change the long-term outcome for the patients and their families.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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