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Take a look at a selection of our recent media coverage:
27th January 2023
A T cell biomarker, represented by low levels of differentiated CD3+CD27–CD28– T cells before leukapheresis could serve as a novel marker to predict an individual’s response to CAR T cell therapy in those with relapsed/refractory diffuse large B cell lymphoma (DLBCL), according to a study by researchers from the Medical University of Vienna, Austria.
Chimeric antigen receptor (CAR) T cell therapy produces a durable response in patients with either relapsed or refractory DLBCL. However, trying to identify which groups of patients are likely to respond to therapy is difficult and currently based on lactate dehydrogenase after lymphodepletion, tumour volume and Eastern Cooperative Oncology Group performance status. Nevertheless, each of these three measures does not relate to the immune system. In the current study, the Austrian team looked at a particular T cell biomarker and made use of a matched group of healthy control patients for comparative purposes.
T cell biomarker and CAR T treatment response
A total of 33 patients (mean age = 61.8 years, 42.4% female) with either relapsed or refractory DLBCL were matched with a health control group of 24 patients (median age = 60, 41.7% female).
When compared to healthy controls, DLBCL patients had significant lymphopenia and a higher frequency of differentiated CD3+CD27–CD28– T cells (28.7% vs 6.6%, p < 0.001). There were 26 patients infused with CAR T cell therapy and the overall response (OR) 3 months after the infusion was 57.7%, with a complete response (CR) seen in 42.3% of patients.
In regression analysis, the Austrian team found that low levels of differentiated CD3+CD27–CD28– T cells (23.3% vs 35.1%) were independently associated with an overall response. In fact, the association was even more evident when patients were stratified by either complete remission or non-complete remission (13.7% vs 37.7%, p = 0.001). Using a cut-off value of below 18% of CD3+CD27–CD28– T cells was highly predictive of a complete response at 12 months (67% vs 13%, p = 0.009).
The authors concluded that a low number of CD3+CD27–CD28– T cells at leukapheresis represented a novel, pre-infusion T cell biomarker that enabled prediction of a CAR T cell response in patients with relapsed or refractory DLBCL.
Worel N et al. The frequency of differentiated CD3+CD27–CD28– T cells predicts response to CART cell therapy in diffuse large B-cell lymphoma. Front Immunol 2023
25th May 2021
Researchers say ‘stem cell memory T-cells’ appear critical in both destroying the cancer at the outset and for long term immune surveillance and exploiting this quality could improve the design and performance of CAR T therapies.
Researchers assessed the cells of patients involved in the CARPALL Phase I Study, which used a new CAR molecule known as CAT-19 developed between UCL Cancer Institute and UCL Great Ormond Street Institute of Child Health, for treatment in children with acute lymphoblastic leukaemia.
The team compared T-cells from patients who still had CAR T-cells detectable in the blood more than two years after their treatment, with individuals who had lost their cells in the one to two months post treatment.
Using a technique called ‘insertion site barcoding’, researchers were able to study the fate of different types of CAR T-cells in patients after they were given.
Corresponding author Professor Persis Amrolia, based at UCL Great Ormond Street Institute of Child Health and Consultant in Bone Marrow Transplant at GOSH, said: “Using this barcoding technique, we were able to see ‘stem cell memory T-cells’ play a central role both during the early anti-leukaemic response and in later immune surveillance, where the body recognises and destroys cancer cells.
“This suggests that this small sub-group of T-cells are critical to the long-term success of the therapy.”
Researchers say, this work indicates that the teams caring for patients could measure the types of CAR T-cells present after some someone has had their anti-leukaemia therapy, to gain an indication of whether they will be able to preserve their CAR T-cells into the future, avoiding relapse.
Professor Amrolia added: “This new insight may help us to improve our CAR T-cell therapy and work out which patients are at a higher risk of relapse and may benefit from a stem cell transplant after CAR T-cell therapy.”
Dr Biasco added: “It was extremely rewarding to see how the application of our new barcoding technology to study CAR T-cells is unveiling such important information about what happens to these cells after they are given to patients. We now plan to expand the technology we established at UCL and validate these findings in larger groups of patients.”
Co-author Dr Martin Pule said: “This research opens up new avenues to improve CAR design and manufacture, improving the performance of CAR T-cell therapy, to achieve a combination of early tumour clearance and long-term protection from relapses in patients with B cell leukaemia.”