New Treatment Saves Children With Terminal Brain Cancer

0:00Alice Klein:This episode is brought to you by Accenture. When your advertising operations fall out of sync, everything else follows. Spotify and Accenture are working together to reinvent the rhythm of ad sales, using automation, analytics, and smarter workflows to simplify campaign delivery and access better data across the business. The result? Less time spent on operations, more time connecting brands with the moments and fandoms that matter most. Learn more at Accenture.com slash Spotify.

0:30James Woodford:Every parent's worst nightmare is their child getting a brain tumour. Brain tumours are the most common type of solid tumour in children and also the most deadly because they're notoriously hard to treat. But happily, there is now some hope on the horizon with a brand new kind of immunotherapy resulting in remarkable recoveries in a handful of children with terminal brain tumours in a small clinical trial. This story is personal for me because my young nephew, Jeremiah, he died 16 years ago from a brain tumour before anything like this was possible. From New Scientist, this is the world, the universe and us.

1:15James Woodford:And I'm reporter James Woodford. I'm joined by my colleague, Alice Klein, who has just written a story about this promising new treatment. Alice, how does this all work?

1:26Alice Klein:Yeah, so the name of the treatment is Tumor-Associated Antigen T-Cell Therapy, which is a bit of a mouthful. So it's called TAAT for short. It basically involves taking a child's immune cells out of their body, training them in the lab to become better and stronger at fighting their brain tumor, and then putting them back into the child.

1:47James Woodford:Okay, because our immune systems do naturally try to fight cancers in the body, right? So sometimes they just need some extra help?

1:55Alice Klein:Yeah, so our immune systems can recognize cancer cells as foreign, and they do naturally try to eliminate them. But unfortunately, cancer cells often have these clever tricks for hiding from the immune system. And also when you get solid tumors, they often form these tough shells around themselves that stop immune cells from getting in. So the basis of immunotherapy is to try to give the immune system a helping hand to overcome these obstacles.

2:23James Woodford:And the most common cancer immunotherapies that people have heard of are things like checkpoint inhibitors and CAR T-cell therapy. They've been around for years now, but they haven't worked that well for brain tumors. Is that right?

2:38Alice Klein:Yeah. So checkpoint inhibitors are drugs that have been great for treating things like skin and lung cancer, but they have a hard time crossing the blood brain barrier and actually getting to brain tumors. And then there's CAR T cell therapy, which involves taking a person's immune cells out and genetically modifying them to give them an artificial boost and putting them back in. And that's been very effective at treating blood cancers, but it hasn't worked that well for solid tumors, unfortunately.

3:04James Woodford:So this new immunotherapy, TAT, T-A-A-T, how is it different?

3:11Alice Klein:So it also involves taking a person's immune cells out, but you don't actually genetically modify them at all. instead you expose them to certain antigens that are found in tumors and these are like little protein markers that act like red flags and signal an attack from immune cells so you find the immune cells called t-cells that are particularly good at recognizing these red flags then you multiply them in the lab to make thousands more and then the last thing you do is to inject these top-notch immune cells back into the person's bloodstream so that they can then go forth and fight the tumor

3:46James Woodford:So TAT isn't approved yet. It's still in early stage clinical trials, but how promising was it in children with brain tumours in this latest trial?

3:58Alice Klein:Yes, so the treatment's been developed by researchers at Children's National, which is a hospital in Washington, D.C. And because it's still, you know, this very early experimental treatment, they decided to first try it with children and young adults who had very, very aggressive brain tumours who'd really run out of other options. quite a few of them had what's called diffuse intrinsic pontine glioma which is this really awful kind of brain cancer that affects the brain stem and it has an average survival of less than a year so there was that group and then others had highly aggressive forms of glioblastoma or modelloblastoma and some had had up to 17 rounds of chemo or radiation or other treatments before having this new experimental treatment and those previous ones hadn't worked so that meant that their prognosis was quite grim.

4:46James Woodford:But this new immunotherapy TAT, did it work for some of these patients? Yeah.

4:52Alice Klein:So there were 33 children and young adults who received the therapy and sadly, most of them did end up dying. But there are four who are still alive between two and five years after they had the treatment. And three of those actually have no evidence of disease. So I think that's pretty amazing considering that they had what were considered these fatal incurable brain tumors and now they're cancer free and they're getting to grow up. And plus, now that there's this proof of concept, it might be possible to refine the therapy further to make it work for even more children with brain tumors.

5:25James Woodford:That must be really incredibly gratifying for the researchers who've been developing this.

5:31Alice Klein:Yeah, well, I spoke to one of the researchers who's been involved in developing this new treatment, Catherine Bollard, and she said she's still in touch with one of the families and they're just incredibly grateful that their child, who they thought they were going to lose, is still with them today many years later.

5:46James Woodford:And what about safety? Since it's an experimental therapy, did it have any unexpected side effects?

5:53Alice Klein:Fortunately, it was mostly well tolerated. Some children got headaches or felt tired afterwards, but they did recover pretty quickly. There were two children who had tumour swelling, but this was thought to be because they already had very large tumour volumes to begin with. So overall, it was seen to be pretty good from a side effect point of view, which is great because other treatments like chemo and CAR-T are known for having some very terrible side effects.

6:20James Woodford:And why is it that TAT, compared to the other treatments, seems to have had fewer side effects?

6:27Alice Klein:It's probably because you're using a patient's own cells. You're not injecting anything foreign like chemo. You're not genetically modifying their cells in any way, as is the case for CAR-T. So I think that's probably the reason why these children's bodies are accepting it a bit better.

6:42James Woodford:Okay, but the trial, you know, we have to acknowledge it was pretty small and it didn't have a control group to compare this new treatment with existing treatments. So how confident can we be that it actually works better and is more tolerated and safe?

7:00Alice Klein:Well, these children had already exhausted all the standard treatments, but you're right, we do need larger clinical trials to really confirm that it does work and is better than existing treatments. I spoke to a pediatric neuro-oncologist in Australia and he said, although no one's jumping up and down and saying this is it just yet, the early results from this trial are encouraging and they open up this whole new potential treatment avenue, which is really important because survival rates for pediatric brain tumors, like they just haven't really budged for at least 20 years.

7:30James Woodford:And a really important question is, are more clinical trials planned? What's next for this group of researchers?

7:36Alice Klein:Yeah, the team is starting two more clinical trials right now, also in children with brain tumors. In the first one, they're combining this TAAT with an ultrasound technique that opens up the blood-brain barrier so that when they inject a child's multiplied T cells back into their bloodstream, hopefully the cells will have a better chance of actually getting into the child's brain to attack their tumor. In the second clinical trial, they're trying this very personalized approach where they take a sample of a child's brain tumor, they analyze it to find out exactly which antigens it contains, and then they tailor the therapy to specifically attack these antigens.

8:13Alice Klein:So instead of just picking, say, three antigens that are common in pediatric brain tumors, they're targeting a child's unique set of tumor antigens. And then finally, in future trials, the team is hoping to combine this TAT with other immunotherapies like checkpoint inhibitors because it's possible that they may have synergistic effects.

8:32James Woodford:And does that mean instead of saving just four out of 33 children with terminal brain cancer, that TAAT might save an even higher proportion?

8:44Alice Klein:Yeah, that's the hope. This episode is brought to you by Accenture. When your advertising operations fall out of sync, everything else follows. Spotify and Accenture are working together to reinvent the rhythm of ad sales, using automation, analytics, and smarter workflows to simplify campaign delivery and access better data across the business. The result? Less time spent on operations, more time connecting brands with the moments and fandoms that matter most. Learn more at Accenture.com slash Spotify.

9:16James Woodford:Why is it that brain tumors are one of the most common types of cancer in children? it just really does seem especially cruel.

9:24Alice Klein:Yeah, I mean, I should say that even though brain tumours are the most common solid tumours in children, they are still rare. They affect about five in every 100 ,000 children. Brain tumours can occur at this young age because they can be a product of random genetic mutations that sometimes arise in cells in an embryo or a fetus rather than being caused by environmental factors like, say, an adult smoking cigarettes for years.

9:47James Woodford:And are there any other promising fronts for treating brain tumours in children?

9:52Alice Klein:Well, on the subject of personalised medicine, which we touched on before, there's actually a nationwide program here in Australia called Xero, which is ambitiously trying to cut the number of childhood cancer deaths to zero. And the way they're trying to do that is by genetically sequencing cancer cells from every child with cancer. And then they look for treatments that can target the cancer's precise drivers. So for example, I've previously interviewed the parents of a boy called Jack who had what was deemed an incurable brain tumor when he was nine, but now he's a healthy teenager after going through this zero program.

10:27James Woodford:Wow. So how did the genetic sequencing allow his recovery?

10:33Alice Klein:It showed that his brain tumor was being driven by this specific mutation in a gene called BRAF. And once the oncologists knew that, they were able to give him these two drugs that are known to target this particular marker. And these two drugs were so successful that within weeks, the tumors in his brain and spine started shrinking. And then they actually did it all together. So he went from not being able to walk at all, being completely bed bound, to playing tennis in the space of four weeks.

11:02James Woodford:That really is incredible. And it's reassuring to know that all this research is going on to try to prevent any child from dying from a brain tumor. As a parent myself, I hope the parents of the future will be spared this never-ending worry about this. That's all for this episode. Thanks to Alice Klein and thanks to you for listening. Do subscribe and follow wherever you get your podcasts. Bye for now.

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