Could a powerful new blood cancer treatment help more patients?
Cancer types:
Lymphoma
Project period:
–
Research institute:
Institute of Molecular Cancer Research
Award amount:
£265,500
Location:
Switzerland
Professor Anne Müller and her team in Switzerland are searching for a way to help more patients with an aggressive blood cancer benefit from a cutting-edge new cancer treatment. Their work will give critical new insights into the disease, and ultimately lead to better therapy options for everyone living with the condition.
Why is this research needed?
Diffuse large B-cell lymphoma (DLBCL) is a fast-growing blood cancer. It causes white blood cells called lymphocytes to grow out of control, and needs very aggressive treatment which sadly, doesn’t always work. DLBCL is also most commonly diagnosed in older adults, and these patients can sometimes find it more difficult to tolerate the aggressive treatment needed.
Excitingly, a new and cutting-edge cancer treatment called CAR T-cell therapy is showing real promise for some people with DLBCL. Although CAR T-cell therapy has some side effects, it is a more gentle option than current standard chemotherapy treatments for DLBCL. But not everyone can benefit, and this is what Professor Anne Müller and her team hope to change.
During this project they will search for new ways to make CAR T-cell therapy more effective in patients with DLBCL, so more people can benefit from this new, kinder, life-saving treatment.
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What is the science behind this project?
CAR T-cell therapy works by engineering the patient’s own white blood cells to target cancer. But some tumours do not respond, and unfortunately for many people with DLBCL, the therapy will fail.
Professor Müller and her team believe this could be to do with a surprising finding that many DLBCL tumours are actually packed with a type of white blood cell called a macrophage. This cell carries a molecule called PDL1 on its surface. Importantly, tantalising early evidence suggests that patients with DLBCL who are less likely to do well with treatment are more likely to have high levels of macrophages and PDL1 in their tumours.
So with this Curestarter funding, the team will figure out in the lab exactly how PDL1 seems to help DLBCL cells grow, and overcome CAR T-cell therapy. As part of this work they will study tumour samples from 30 to 40 patients with DLBCL who are about to start CAR T-cell therapy, and measure their levels of PDL1 carrying macrophages. This will help the team to understand exactly how PDL1 levels might be linked to treatment success.
By the end of the project the team hope to know a lot more about why CAR T-cell therapy does not work for some patients, and also who is most likely to benefit. They also hope to identify new ways to ‘switch-off’ PDL1 macrophages, that could be used either alone or alongside CAR T-cell therapy to boost patient response.
What difference could this project make to patients in the future?
DLBCL is the most common form of non-Hodgkin lymphoma, and about 5,000 people are diagnosed with the condition every year in the UK - mostly older adults.
Professor Müller and her team are working to make CAR T-cell therapy, a new and kinder type of treatment, more effective for patients with DLBCL. They hope to uncover new signals that could be used by doctors to predict who is most likely to respond to therapy, and also identify new approaches that could potentially be used alongside CAR T-cell therapy to make it more effective. Ultimately, the team hope that findings from this project will help more people gain more benefit from this newer, kinder, cutting-edge therapy.
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