In the news: re-tooling the body’s police force to beat leukaemia

Our internal police force can be enhanced

Our immune system is our very own internal ‘police force’. It’s made up of disease-battling cells and proteins that travel through our bloodstream, searching out potentially harmful infections like the flu.

In the past couple decades, the immune system’s role in cancer has come into sharp focus, and a whole scientific field of cancer immunotherapy has developed.

Immunotherapy’s goal is compelling – to coordinate and re-tool the body’s police force so that it’s better equipped to seek out and destroy cancer cells. And we’ve written before about how immunotherapy is inching closer to being fully deployed in hospitals and clinics.

Last week, there was a flurry of coverage of a new immunotherapy treatment for leukaemia that “blows tumours away in weeks”.

Exciting headlines, but what does the science say on closer inspection?

We spoke with Dr Caetano Reis e Sousa, a Cancer Research UK immunotherapy expert, who was very upbeat about the research, but was also quick to caution that much larger trials are needed before we know for sure how effective and safe this experimental approach will prove to be.

A crash course in immunotherapy

Like many scientists, immunotherapy experts use a lot of technical jargon – simply because our immune system has so many different parts that need describing. Just like a police force is made up constables, detectives, lieutenants, and their many tools of the trade – truncheons, handcuffs, walkie-talkies, etc – our immune system is composed of a complex network of different cells and their tools.

The study that hit the headlines last week looked at an experimental immunotherapy treatment for chronic lymphocytic leukaemia (CLL). This is a cancer of B-cells, specialised immune cells that normally help to fight off disease by pumping out proteins called antibodies into our bloodstream to fight disease.

There are a whole host of other cells and proteins involved in immune responses, but they can be distilled into some key heroes and villains in this particular ‘shoot out’:

• T-cells: also part of the immune system police team, these specialised cells don’t pump out antibodies, but instead have inbuilt tools (receptors) on their surface that seek out disease ‘criminals’.
• Antigens: these are what the immune system is looking for – small protein clues to the criminal’s presence in the body.
• Antigen receptors: these are the tools that T-cells use to home in on antigens – they’re like miniature radar-dishes studded on the T-cells’ surface, able to detect even tiny amounts of antigen.

Designer cells

Dr Reis e Sousa explained that researchers have long been trying to harness the disease-killing power of T-cells, and that it is only recently that they’ve had some clinical successes.

He says some of the first positive results appeared a few years ago in patients with metastatic melanoma, the most serious form of skin cancer.

These successes are thanks to new techniques to genetically engineer designer T-cells, effectively re-programming them to attack specific types of cancer cell.

In this most recent study, the scientists engineered T-cells to carry a special ‘cancer-seeking’ antigen receptor. The receptor is made up of a combination of carefully selected protein parts that together cause it to home in and destroy cancerous B-cells.

Such engineered receptors are called ‘chimeric antigen receptors’, after the Chimera, a mythical fire-breathing animal with a lion’s head, a goat’s body, and a serpent’s tail.

Impressive (but early) results

Following years of painstaking lab work, the scientists were finally able to start a very small (Phase I) clinical trial of their engineered T-cells. Phase I trials are primarily designed to see if a treatment is safe. People taking part in Phase I trials often have advanced cancer and have usually had all the treatment available to them.

The researchers recruited three elderly patients with advanced CLL whose disease was resistant to several other standard treatments. The patients were given very small doses of the engineered T-cells.

Between 7 to 21 days after receiving the T-cells, each of the patients developed quite serious fever and other side effects such as nausea, which led them to being monitored in hospital.

Although of course unpleasant for the patients, and worrying for their relatives, these particular side effects were actually a key sign that the treatment was working. They were a result of the tumour cells being blown apart by the treatment and their building blocks spilling out into the bloodstream. As one article last week described it, the symptoms were the cancer’s “dying scream”.

Within weeks, two of the patients’ cancers had been completely destroyed, and the third patient had a partial response to the therapy. The researchers calculate that for every individual T-cell injected into the patients’ bloodstreams, around 1,000 tumour cells were killed. And crucially, several months later the effects of the treatment have continued – for two of the patients this means they are still completely cancer free.

Dr Reis e Sousa thinks these are “truly impressive results”. But he’s also been working on immunotherapy long enough to know that we shouldn’t get carried away just yet.

These are early days, and there’s a lot more work to do to understand the effects of these engineered T-cells on the body, he says. For example, the research also showed that the engineered T-cells also attacked some healthy cells in the body – this could potentially cause long-term complications, and the researchers urgently need to know more about such effects before a treatment could be given outside a research environment.

And it’s also a mystery why two patients responded so well, whereas the third fared less well – this is a question that also needs answering.

Optimism for the future

Overall, Dr Reis e Sousa is cautiously optimistic about this work. He says that the immune system is equipped with countless tools to fight cancer, and that this research is among a growing body of work showing that scientists are finally finding ways to manipulate these tools into ‘smart drugs’ to fight cancer.

At the end of our conversation, before he left us to get on with his own work to harness the immune system to treat cancer, Dr Reis e Sousa said he thinks that “immunotherapy is finally coming of age.”

We hope so, and with the incredible support of the public, we plan to be a big part of this.

Oliver Childs

References

Porter DL, Levine BL, Kalos M, Bagg A, & June CH (2011). Chimeric Antigen Receptor-Modified T Cells in Chronic Lymphoid Leukemia. The New England journal of medicine PMID: 21830940

Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, & June CH (2011). T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Science translational medicine, 3 (95) PMID: 21832238