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Catching a glimpse of cancer-killing immune cells

Your immune system is a wonderful thing. Ultimately, it keeps you alive, fighting off infection from a range of invaders such as bacteria, viruses and parasites. Your immune system also does a good job at culling cells that are at risk of becoming cancerous. But cancer cells are clever. They learn to adapt, and sometimes they evolve ways to hide from the immune system, blending in amongst healthy cells and going undetected.

But scientists are smarter. Research over the years has led us to a point where we have developed increasingly clever ways to pull down the defences deployed by cancer cells. Recently, we have witnessed new therapies used in the clinic with unprecedented success that focus on exposing cancer cells to the patient’s own immune system. CAR T-cell therapy is one of these successes.

T-cells are a type of cell that make up your immune system. They are the attack dogs of the immune system, sniffing out trespassers and eradicating them before they can do any damage. A CAR T-cell is a T-cell that has been genetically engineered by scientists in the lab to be able to recognise cells from a patient’s tumour. CAR T-cell therapy involves taking a sample of blood from the patient and isolating their T-cells from the rest of the blood. The patients T-cells are then genetically engineered to recognise a specific feature of the patient’s tumour cells. The patients pumped-up T-cells are then allowed to replicate in the lab until there is an army of them ready to be transplanted back into the patient where they can get to work attacking the tumour.

Dr John Maher, a researcher and clinician from King’s College London, who leads a research team focussed on developing CAR T-cell therapies, said: “CAR T-cell therapy has proven to be a game changer in the treatment of blood cancers. However, impact on solid tumours, such as lung or prostate, has been less impressive. This represents the next frontier in the clinical development of this new type of cancer treatment.”

Dr Maher’s recent work, funded by supporters of Worldwide Cancer Research, has been looking at new ways to visualise CAR T-cells as they travel around a patient’s body looking for tumours. “Live Imaging of CAR T-cells gives us the opportunity to see where in the body these cells are ending up, both at tumour sites and normal organs and tissues of the body. This technology will help us understand better how the distribution of CAR T-cells in the body relates to how well a patient responds to therapy, as well as insights into any adverse side effects of the treatment”, explained Dr Maher.

Research published in March by Dr Maher’s group, working in collaboration with co-senior author Dr Sophie Papa, describes a new way to image CAR T-cells in live animals over time using imaging technology commonly found in hospitals. The team genetically engineered CAR T-cells to incorporate a gate-like molecule on their surface that allows a special imaging chemical to pass through into the CAR T-cell. Once both the CAR T-cell and the imaging chemical are injected into the animal they can watch where the cells end up using imaging techniques similar to a CT or X-ray scan.

Although this has only be shown in mice, all the components of the technique, such as the imaging chemical used and the engineering of CAR T-cells, are already used in patients, so it is expected that the findings could be translated to the clinic easily. Speaking about the potential immediate impact of their work, Dr Maher said:

“We are currently running a Phase I CAR T-cell trial in patients with head and neck cancer where we are using imaging to track their location of CAR T-cells after they are injected into the patient. The new imaging techniques we recently reported would now allow us to repeat the imaging at later time points. This could be important, for example, if a patient developed signs of progressive disease or treatment-related toxicity. Knowledge of the location and number of the CAR T-cells at that time could be very helpful in guiding clinicians to distinguish between these possibilities. Imaging is also non-invasive so it would also spare patients from the need to undergo tissue biopsy procedures.”

This type of treatment for cancer is truly revolutionary. It has proved successful for treating blood cancer and has even led to complete remission in some patients. It is only through continued research that we will see this success replicated in other cancer types. Dr Maher said:

“We are extremely grateful to the supporters of Worldwide Cancer Research for funding our research. An Improved understanding of cancer and development of better treatments for these diseases relies fundamentally on your generosity”.

The full research article is available online: https://www.nature.com/articles/s41467-018-03524-1

Science Communications Manager

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