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The next generation of CAR T-cell therapy
Tomorrow
Training immune cells to recognise, hunt down and destroy cancer cells – known as CAR T-cell therapy – has shown promise in treating childhood leukaemia (see page 24). But some key challenges remain.
Cancer cells can evolve in response to the treatment, putting up defences that make CAR T-cells less effective. Dr Sara Ghorashian says: “They produce blocking substances or change the way they appear in an attempt to escape recognition by the CAR T-cells.
“We’re developing a new generation of CAR T-cells, engineered in the laboratory to carry extra ‘equipment’ that will help them keep going, even when the tumour is trying to stop them doing their job.” One of these new weapons is an ability to recognise more than one unique marker on the surface of cancer cells. That means if the cancer cells evolve to shed one marker, the CAR T-cells should still be able to lock onto their target.
Another challenge is cases where patients are too ill to spare their own T-cells. Sadly, these patients currently have little hope of recovery. But Professor Waseem Qasim hopes to change that: “We’re creating ‘universal’ CAR-T cells, known as UCART. These are sourced from volunteer donors but modified so they can be used without being specifically matched to the child. We successfully treated the first child in the world with these cells in 2015.”
Another key area of research is improving manufacturing techniques, to ensure CAR T-cells can be made in large volumes. GOSH researchers are working hard to create CAR T-cells targeted at other life-threatening cancers.
2020 The next phase of the CARPALL study will open, using more advanced CAR T-cells engineered to recognise an additional target on the surface of leukaemia cells.
How CAR-T therapy works
1. Immune cells don’t recognise that cancer cells are harmful.
2. In CAR-T therapy, immune cells are taken from the patient and engineered to recognise cancer cells. Immune cells Cancer cells
3. When given back to the patient, these engineered cells can then recognise and destroy cancer cells.
