Fighting Brain Tumours with Artificial Antibodies
A new way to tackle brain tumours has been tested successfully in mice by researchers in the US. The team at Stanford, in California, have found a way to trigger the immune system to selectively attack cancer cells but leave healthy brain tissue untouched. The discovery hinges on a signal called CD47, which brain tumours display on their surfaces. This is an immune off-switch, which sends out a kind of “don’t eat me” signal that prevents the dangerous cells from being destroyed. But an artificially-produced antibody that blocks this CD47 signal can save mice with otherwise lethal human brain tumours. Chris spoke to neurosurgeon Samuel Cheshier to hear how…
Samuel - Brain cancer is the number one killer of children of all cancers and it’s tough to treat because one: a lot of times we can’t operate to take out the cancer tissue mainly because the brain is a very sensitive organ and there’s lots of it you can’t touch. And the other issue is the brain greatly regulates what gets in it from the outside so it’s very difficult to get drugs into the brain.
And finally, some of the treatments that we do have that can treat brain cancer effectively, they’re all just a little bit more poisonous to the cancer than it is to the person. They have a lot of toxic side effects because children are growing and developing they're even more susceptible to the side effects than adults. So you can treat a brain cancer, but take a child who would be going to Oxford and Cambridge and change that person to someone who can’t even ever hold a job.
Chris - I’m glad you didn’t name any other rival institutions because they would feel second best. But what is the approach that you think we might be able to take then if surgery isn’t an option and current chemotherapy regiments are just too vicious? What could we do instead?
Samuel - What we can do instead is to get your own body to fight the cancer, and the main part of the body that is really capable of doing that is the immune system. Now normally your immune system actually fights colds, and flu, and fevers, and bacteria, and germs, and things of that nature, but what you might not know is your immune system actually fights cancer cells as well. There are some estimates that every single day your immune system takes care of one to five cancer cells and gets rid of them. But what happens when your cancer is able to grow is that the cancer sends out signals that trick the immune system into leaving it alone. And what we’re doing here is we’re using special proteins to subvert the cancer tricking in order to get your own immune system to go ahead and attack the tumour again and kill it.
Chris - Effectively the cancer is disguising itself and saying “look, I’m healthy, don’t eat me, I’m harmless”?
Samuel - That’s exactly what’s going on. The immune system can kill a cancer in three ways - one is to target it like a smart missile and explode it. The other one is to touch it and kill it sort of like what Dr Spock does in Star Trek, where he hits you with the Vulcan death grip and then you just fall down. T cells do that. And the cells that we use in our experiments are called macrophages. They’re really like the Pac-Mans of the immune system and they’re capable of eating cancer cells. But what happens is cancer express a special protein on the surface of the cell that says “don’t eat me,” and when we subvert that process by a protein called anti-CD47, the “don’t eat me” signal becomes unreleased and the Pac-Man can now eat the cancer cell. So, if you think about it, if anyone’s ever played Pac-Man, the anti-CD47 is that big power pill that Pac-Man eats and now can eat the ghosts.
Chris - So talk me through the experiments that you’ve done then to show that this can work and how you actually came up with something that’s capable of masking that “don’t eat me” signal?
Samuel - This was actually a collaboration between a number of scientists at Stanford University. We took actual pediatric brain tumours from patients that we had operated on and we put them in brains of mice that were genetically engineered to be capable of receiving human tissue. The tumours grew in the brains of the mice and we gave them the drug and the tumours went away. The other thing that was really cool is that we put normal human brain cells with the brain tumours and even with active eating of the brain tumours, the normal human brain cells that weren’t cancerous continued to grow and thrive in the setting of excellent tumour killing.
Chris - So what actually happened in the mice then, were they completely cured?
Samuel - Our mice, if you had received the treatment, they all lived and they lived for a very long period of time. Every mouse that didn’t receive the treatment died.
Chris - One of the things that cancers notoriously do is spread. Presumably, because you’re bringing the immune system to bear against the tumour, it doesn’t matter if it’s spread because this drug will go to wherever it’s spread to and make the immune system active in that place too?
Samuel - That’s absolutely true, and one of the tumours that we treated was called a medulloblastoma. This brain tumour has a very big propensity to spread all around your brain, and what we learned is not only can the anti-CD47 treat the primary tumour growing in the brain, but all the spread up and down the brain and the spinal cord was also treated as well.
Chris - Is it relatively easy to now translate this antibody that you’ve made, this artificial antibody that hits this “don’t eat me” signal to human patients to try it in them?
Samuel - Absolutely. Actually, we are using this particular monochromic antibody in patients with cancers in the very earliest stages of clinical trials.