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Extra chemo boosts immune cell therapy in lymphoma

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by In collaboration with PA Media Group | News

8 September 2016

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Human T cell.

Using two chemotherapy drugs instead of one may boost the effectiveness of a type of immune cell therapy, according to a new US study

“This is important because it will help guide the design of future trials using these specialised T cells” – Professor John Anderson, UCL Great Ormond Street Institute of Child Health.

The early clinical trial showed better responses and improved short-term survival in patients with non Hodgkin lymphoma given the combined treatments. 

Published in the journal Science Translational Medicine, the findings could also have important implications for future trials involving so-called CAR-T cell therapy.

The approach involves removing specialised immune cells, called T cells, from a patient and engineering them so that they recognise and kill cancer cells when reintroduced into the patient. 

In the new clinical trial, involving 32 patients with advanced non-Hodgkin lymphoma, the researchers selected specific types of T cells to reengineer. Patients were then either given the chemotherapy drug cyclophosphamide alone, or in combination with a different drug called fludarabine. 

According to the researchers, based at the Fred Hutchinson Cancer Research Center and University of Washington, the combined chemotherapy produced stronger cancer killing effects from the immune cells.

Dr Cameron Turtle, one of the lead researchers of the study, said that refining the treatment approach in this way “can have a big impact on clinical outcome.”

After treatment, half of the patients given fludarabine saw all signs of their disease disappear. This was compared to eight per cent of patients who did not receive fludarabine. 

Professor John Anderson, an expert in immunotherapy from UCL Great Ormond Street Institute of Child Health, said: “This is the first clinical trial to show multiple benefits from adding fludarabine to cyclophosphamide when preparing non Hodgkin lymphoma patients for this type of immunotherapy. This included fewer side effects and improved responses. 

“This is important because it will help guide the design of future trials using these specialised T cells. But it could also have implications for the CAR T cell therapy field in general, especially as researchers look to test them in more types of cancer. 

“We still don’t know how precisely fludarabine works in preparing the body to receive T cells, so more work is needed to look into this alongside further clinical trials.”

The findings suggest that perfecting the combination of chemotherapy and immune cells is vital to unlocking the full potential of CAR-T cell therapies. 

While fludarabine was linked with worse side effects, the researchers detected molecular ‘signatures’ in the patients’ blood that could indicate that a patient may experience side effects following immune cell treatment. This could provide a means of identifying high-risk patients who may benefit from having their treatment stopped.

Turtle, C. J. et al. (2016). Immunotherapy of non-Hodgkin’s lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor–modified T cells. Science Translational Medicine. 8 (355).