Fire with fire

Although the real science is fascinating, doctors didn't "inject HIV into a dying child"

We’ve recently noticed an inspiring short film circulating on the internet about how doctors in the US have apparently cured a child of leukaemia by “injecting her with HIV”.

But while the actual science behind this story is fascinating, the treatment is still at an extremely experimental stage and has only been tested in a handful of patients.

And while we’re always keen to welcome exciting experimental cancer treatments, we also want to clear up a few misconceptions about what the research actually involved.

To be absolutely clear, the doctors in the video did NOT inject HIV – nor a “deadly disease” – into a child.

So who are these people, and what did they actually do?

[Note – the headline of the Upworthy page hosting the video has now been changed to reflect that it was a modified form of HIV. KA 13/05/14]

Turning the immune system on cancer

The research comes from Professor Carl H. June and his team in Philadelphia in the US. He’s a highly-respected scientist working on cancer, HIV and the immune system, and has published his work in hundreds of papers in many leading scientific journals over several decades.

The immune system is an incredibly hot topic in cancer research. Cancer is an illness that starts from our own cells going rogue within us. Our immune system is pretty good at recognising and attacking foreign invaders – such as bacteria or viruses – but it doesn’t do so well at tackling tumours.

A huge amount of research effort around the world is focused on trying to understand why the immune system doesn’t recognise and fight off the disease. And there’s also a lot of work aimed at harnessing this powerful force for treating cancer, and this is leading to new ways to treat the disease.

Professor June and his team are taking an interesting approach to this challenge. In particular, they’re developing new ways to turn the power of the immune system on leukaemia – a cancer caused by white blood cells (usually B cells, also part of the immune system themselves) growing out of control.

They’ve developed a technique in which they collect special ‘killer’ immune cells, called T cells, from a cancer patient. These are then ‘reprogrammed’ in the lab using a modified virus, which is very good at smuggling genes into the T cells.

In this case, the researchers added genes carrying instructions that tell the T cells to make a new protein called a “chimeric antigen receptor” – this lets them lock on to molecules found on the surface of cancer cells, killing them in the process.

These reprogrammed T cells are then injected back into the patient, where they grow and multiply, creating an army of killer cells to fight the disease.

At least, that’s the theory.

From the lab to the clinic

The Philadelphia team has been working on this technique for many years, developing it first in the lab then testing it in animals with promising results. They’re now taking this a step forward, into clinical trials with cancer patients.

The situation described in the video, where a little girl called Emily Whitehead (referred to as Emma in the film) undergoes modified T cell treatment, isn’t the first time this approach has been tested in people. There’s more than a decade’s worth of data looking at the safety and effectiveness of virus-modified T cells in clinical trials for treating people with HIV as well as cancer.

In 2011, Professor June’s team treated three adults with chronic lymphocytic leukaemia (CLL) with virus-modified immune cells as part of a small, early-stage clinical trial. All three had undergone several rounds of chemotherapy, yet their cancer kept coming back. For two of them, their cancer completely went away after the T cell therapy – something known as “complete remission”. This was an important and impressive result, although one that was probably over-hyped in the media at the time.

Further results from the trial – totalling 10 adult patients with CLL and two children with a different type of leukaemia (acute lymphoblastic leukaemia, or ALL) were announced at a scientific conference at the end of 2012. The researchers claimed that nine out of the twelve patients had been treated successfully – presumably three of the adult patients are from the 2011 paper, while the two children are likely to be from the paper we’ll discuss shortly.

And in March this year, a team at Memorial Sloan-Kettering Cancer Centre in New York published results testing a similar approach in five adults with ALL. In all five, the cancer vanished, although four of them went on to have further treatment so it’s hard to say whether this therapy was solely responsible for curing them. And for the final patient, the cancer came back once the reprogrammed T cells had died off in their body.

From what we can tell, the girl in the video – Emily/Emma – is being treated as part of another small-scale, early-stage clinical trial for children with leukaemia and lymphoma, testing the virus-modified T cell treatment. This is primarily a trial to find out whether the treatment is safe, rather than how well it works.

Results from two children with ALL were recently published in a paper in the New England Journal of Medicine. Of the two kids, one seems to have had a complete remission – we can only assume this might be Emily, though she isn’t mentioned by name in the paper. Sadly, the other child didn’t do so well. The cancer came back just two months after the T cell treatment.

Obviously, for Emily and her family this experimental therapy has been nothing short of a miracle. But from the handful of cancer patients treated so far, it’s clear that it doesn’t work for everyone – something that’s rightly pointed out in the film.

The therapy also causes significant side effects, dramatically described in the video. Several of the patients who receive the modified T cells seem to experience what’s known as a “cytokine storm” – a potentially fatal immune reaction. Subjecting weakened cancer patients to such a barrage is highly risky, so researchers need to proceed with great caution as the clinical trials continue recruiting patients.

How does HIV fit into the picture?

Promoting the video, the Upworthy website boldly states that the doctors are injecting “HIV into a dying girl”, and that she received a “deadly disease”. This is a serious bending of scientific truth, and very misleading.

In fact, the researchers are using a type of virus called a lentivirus to reprogramme the T cells. This family of viruses – of which HIV is a member – are particularly skilled at sneaking into cells and embedding their genetic code within the cell’s DNA. Unsurprisingly, this makes them a good vehicle for smuggling in the genetic instruction telling T cells to attack the cancer.

According to the video, Professor June says that the virus used in these experiments was originally derived from HIV, and we hear the film-maker asking off-camera “So you’re taking the HIV virus and infecting healthy cells with it to help kill cancer?” However, the virus has undergone significant genetic tinkering, meaning that it is no longer harmful (as June does go on to explain). And it’s arguable whether it should even be referred to as HIV at all, given how much it has been altered.

And the researchers didn’t inject any virus into anyone. As we’ve explained, they took immune cells out of the patient, treated them with the virus in the lab, then injected the modified cells back in.

To sum up

Broadly speaking, we feel that this film is inspiring, and we’re always happy to see the fruits of promising new therapies for cancer. But to promote “injecting HIV” as a treatment is misleading.

One child surviving ‘incurable’ cancer is an amazing event, but there is a lot more work to be done to find out how best to use this new technology. At the moment it’s still highly experimental and expensive. It’s only being trialled in a very small number of patients, primarily to make sure it is safe, and so far we’ve seen that it doesn’t work for everyone.

In the case of the child whose cancer came back after treatment, the researchers found that her cancer cells had somehow stopped carrying the T cells’ target molecule. So it’s likely that other targets will need to be identified, to make the treatment more effective for more patients in the future.

On a positive note, there’s no reason why this type of treatment should be restricted to cancers affecting the immune system (namely leukaemia and lymphoma), although they’re much more accessible to the killer T cells. Researchers elsewhere are investigating how to target a range of different types of cancer with this approach.

There are several similar therapies being tested in the lab and in clinical trials around the world, including in the UK. And Cancer Research UK scientists are finding out whether harmless genetically-engineered viruses could be used as therapeutic vaccines, training the immune system to seek and destroy cancer cells.

It’s still early days for these exciting new approaches and there are many hurdles to jump, but we’re looking forward to the day when they can be used to treat patients on a wider scale.

Kat

Reference:

Grupp S.A. et al (2013). Chimeric antigen receptor-modified T cells for acute lymphoid leukemia., The New England journal of medicine, PMID:

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Cancer genes Cancer in the news Children and young people's cancers Immune system Immunotherapy Leukaemia Research and trials Treatment