Posted On: December 21, 2018
So-called CAR-T cell therapy is a promising option for treating around a fifth of patients with diffuse large B-cell lymphoma. That is the main finding of the multi-centre JULIET study, in which researchers from the Comprehensive Cancer Centre (CCC) of MedUni Vienna/Vienna General Hospital participated, and will continue with an expanded investigation to include a leading children's hospital.
In CAR-T cell therapy, previously modified T-cells recognise a specific protein on the surface of the tumour. This in turn triggers destruction of the tumour cells. This introduces a new option for treating patients diagnosed with large B-cell lymphoma, besides the conventional standard treatment (chemotherapy). This is because the two-year survival rate following standard treatment is only 20 per cent, whereas, with CAR-T cell therapy, overall survival was doubled to 40 per cent. The results of the JULIET study have now been published in the prestigious "New England Journal of Medicine".
Read more: Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma.
With 480 new cases a year, diffuse large cell B-cell lymphoma is most common type of lymphoma (cancer of the lymph cells) in Austria. Moreover, it is a very aggressive disease, which is normally treated with a combination of chemotherapy and immunotherapy. Around 50 per cent of cases are permanently cured with this regime, however, the other half suffer relapse and to-date there has been no satisfactory treatment.
Immune system permanently modified
A potential new treatment could now help these people: CAR-T cell therapy. This is a targeted therapy directed against the protein CD19, which is found on the surface of tumour cells in 90 per cent of relapsed patients.
In CAR-T cell therapy, the T-cells are removed by blood dialysis and genetically modified in a special device - a receptor capable of docking onto CD19 is attached to their surface. In the third stage of the therapy modified T-cells are multiplied and returned to the patient by infusion. The modified T-cells are now able to recognise the tumour cells and so destroy them. Since the T-cells remain in the body and continue to multiply, they are permanently available to recognise and destroy newly occurring cancer cells with the surface characteristic CD19.
Read more: Using targeted chemotherapies to reduce intensity of radiotherapy in medulloblastoma.
Ulrich Jäger, Head of the Division of Hematology and Hemastasology at the Department of Medicine I of MedUni Vienna/Vienna General Hospital, member of the CCC and principal investigator of the JULIET study in Austria commented.
"Our study shows that CAR-T cell therapy is a ground-breaking treatment option that enables us to permanently cure the disease, even in previously hopeless cases," he said.
Special know-how required
Since CAR-T cell therapy provokes a strong immune response, the treatment is administered on an in-patient basis, so that patients can be closely monitored.
“The procedure is very complex and can only be implemented in an interdisciplinary context,” said Jäger. “MedUni Vienna is one of the few centres in Europe capable of performing this treatment."
"We are therefore maintaining an active scientific exchange with other centres. These include, for example, St Anna Children's Cancer Research in the field of CAR-T cell therapy for childhood leukaemia,” he said.
The next steps
The next goal for the researchers led by Ulrich Jäger is to find out why 40 per cent of patients respond to CAR-T cell therapy, and are cured, while the remaining 60 per cent do not; and, of course, how this situation can be rectified. It is planned to conduct a study into this, building on the JULIET study.
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