Umbilical cord blood stem cells cure HIV case

A new treatment has proveded the 4th ever recorded cure of HIV.
17 March 2023

Interview with 

Ravi Gupta, University of Cambridge


A greyscale computer image of a HIV virus particle


A woman in America has become the fourth person to be potentially cured of HIV when she underwent an immune cell transplant procedure to treat a blood cancer that she’d also developed. Speaking at a press conference as the results were unveiled, UCLA infectious diseases specialist Yvonne Bryson, who led the team treating the patient, was cautiously optimistic about the results…

Yvonne - We have not been able to detect virus in the blood and also her cells are resistant now. She's clinically healthy, free of both cancer and HIV, and we are calling this a possible cure waiting on a longer period of follow up.

Three male patients have previously also been cured of HIV in a similar way. One of them, Adam Castillejo, dubbed “The London Patient”, was on this programme 2 years ago alongside Cambridge infectious diseases doctor, Ravi Gupta, one of the team who helped to effect his cure. Ravi’s back with us today to explain a bit more about this announcement from the US. But before we get into what they did,  why HIV is so hard to cure in the first place?

Ravi - So one of the hallmarks of HIV is that it actually, as part of its life cycle, integrates itself or becomes part of your genetic material in the immune cells which it's infecting. And that makes it really hard to remove it. The only way that the viruses code can be removed is by the cell dying. And so that's why the virus is really, really hard to cure. It can be controlled, but it is really hard to remove genetic material from all of your cells.

Chris - And when you cured Adam, how did you do that?

Ravi - Well, Adam was living with HIV and his immune system had suffered quite badly. And as a result, he developed a cancer that needed a transplant in order to cure it, what we call an unrelated stem cell transplant, where the cells from another person are used to replace Adam's own blood cells. But to do that, you've got to remove Adam's own immune system and blood cells using chemotherapy, which can be quite dangerous. So the interesting thing that was achieved was, which is that we found a donor who had a special mutation in one of the target proteins for HIV and that mutation allows you to become resistant to HIV. And we replaced Adam's cells with these new cells that not only cured his cancer but also made him resistant to HIV.

Chris - Is that mutation naturally present in the population then, there are people out there who are naturally resistant to HIV?

Ravi - Yes. So, in particular Europeans have this mutation called the Delta 32 mutation. Around 1% of Caucasians will have both of their copies mutated. And so that's one in a hundred, which across millions of people, uh, amounts to a fair number of potential donors.

Chris - And they're uninfectable?

Ravi - That's right. They're uninfectable with the strain of HIV that commonly circulates. There are variations of HIV that will get around that mutation but they're less common than the standard variant.

Chris - And so in Adam's case, by giving him cells that make it bone marrow and cells that therefore make an immune system that have or carry those changes, he ends up with a new immune system that cannot be infected with HIV.

Ravi - That's right. So we believe the cancer chemotherapy also helps to kill the HIV infected cells. And actually then the new cells that come in cannot be infected. And so you end up with a situation where the infected cells have died and there are no new possibilities for infection of fresh cells.

Chris - The paper that's been published in the journal cell with Yvonne Bryson, who we heard at the beginning there, describing how they've cured their patient, this woman, the first woman to affect a cure, they're saying they've done it slightly differently than your approach. They're using what they call umbilical cord blood stem cells. So what's the difference?

Ravi - The stem cells that we were using were from adult donors. The paper that we are discussing here involved umbilical cord cells. So these are cells from babies or neonates, and they are taken for future use potentially, for either themselves or other individuals for the purpose of curing various diseases including cancers. So the difference there is that you're taking similar cells, but from much younger humans.

Chris - But apparently they're much more comfortable grafting their way into a person who's a less close match. I think that's the attraction, isn't it, of using those cord blood cells?

Ravi - Yes, apparently. That's right. So, you can get away with a poorer match if you use those types of cells.

Chris - So what are the implications of this? Now, this is patient potentially number four.

Ravi - The main implications are, first of all, it shows that you can achieve a cure in different ways. Secondly, it shows that the CCR5 gene target is a really important one. Because we've now had four examples. And then I think there's an interesting sort of racial slant to this, which is that with this new approach I'm quite pleased to see that actually you can expand the numbers. The sort of people who could benefit from a cure or a curative approach. And that really, I think is really important in this day and age where the vast burden, the vast majority of people living with HIV are not in Europe anymore. So I think that's important for us.

Chris - There's some 38 million people currently infected with the disease and we've cured four of them. Do you think this is a realistic prospect as a way forward? Or is this just an academic interest and great news for the people for whom it works, but it's really beyond the reach of those 38 million?

Ravi - Most treatments start out being tested in small numbers, in what we call pilot studies. And, so you might sort of see this as a pilot study of a test of principle. And of course what we really want to do is to be able to take cells, mutate them to make them resistant to HIV and then give them to a person living with HIV, but without giving them strong chemotherapy that can weaken their immune system and make them vulnerable to quite dangerous infections. So the immune suppression side of this is really where, where the next kind of frontier is going to be.

Chris - Well, I was gonna ask you that because surely doesn't this now say, well the next step would be to get stem cells from a person, their own stem cells, that we can prove they haven't got HIV in them and then just, just do gene editing? I say just, making it sound really easy, but we've got the tools now to genetically engineer the sort of changes into a person's cells to make it as though they were naturally a carrier of this CCR five, delta 32 mutation that gives you the resistance to HIV.

Ravi - That's an excellent point. So that's been the focus of intensive research over the last decade or more where people have tried different gene editing, editing strategies to do the thing you're saying, which is to make the mutation. The difficulty has been the efficiency of that editing has been one of the frontiers. So if you take a hundred cells, maybe only 80 of them would get edited, and so you'd still have 20 that were normal. And what would happen is if you put those back into a person, that those 20 potentially could take over in the patient and then therefore that patient would still be susceptible to HIV. So it's about getting from 80%, um, editing efficiency to 99.999.

Chris - So there's somewhere to go. But it's exciting all the same, isn't it?

Ravi - Absolutely, very exciting for me.


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