Safer and more efficient
Acute lymphoblastic leukemia (ALL) affects about 400 children a year in the UK. Most patients are cured by standard methods of treatment (chemotherapy and bone marrow transplantation), but some patients relapse. CAR T-lymphocytes have shown their effectiveness in relapsing ALL – the most common cause of death from cancer in children in the UK.
In the CARPALL study conducted by Professor Persis Amrolia and his colleagues from University College London, a new type of CAR T-cell therapy was tested in children and adolescents with recurrent ALL.
In CAR T therapy, immune cells (T-lymphocytes) are modified so that the CAR protein (chimeric antigen receptor) is located on their surface, which can specifically recognize tumor cells.
The peculiarity of the new approach is the genetic modification of T-lymphocytes: a specially developed type of CAR molecule, called CAT-19, is located on their surface.
Modified CAT-19 CAR T-lymphocytes were injected into 14 patients with recurrent ALL who are being treated in three children's hospitals in the UK. As a result of therapy, 12 out of 14 patients with incurable other methods of ALL achieved stable remission after three months, five patients recovered. The one-year overall and relapse-free survival rates were 63% and 46%, respectively. The frequency of a dangerous side effect – cytokine release syndrome, or cytokine storm, has decreased.
In an in vitro study, CAT-19 CAR T cells were able to actively divide after meeting with leukemia cells, unlike other types of CAR T therapy. A sufficiently large number of CAT-19 CAR T cells were present in the patients' blood even after the tumor cells were destroyed. This allowed the body to continue to fight ALL years after treatment and avoid relapse.
One of the formidable side effects of CAR T therapy is cytokine release syndrome. It develops as a result of excessive activity of the immune system fighting tumor cells, and can lead to hospitalization in the intensive care unit and even death of the patient. To avoid this, the therapy used in the CARPALL study was designed in such a way that modified T-lymphocytes interact with tumor cells faster than with other similar methods of treatment. That is, CAT-19 CAR-T lymphocytes are able to quickly and effectively destroy leukemic cells and at the same time cause less activation of the immune system, hence fewer side effects. None of the patients who received the new therapy developed severe cytokine release syndrome, which means that this treatment is safer than other types of CAR T-cell therapy. The results obtained need to be confirmed in larger clinical trials.
The authors hope that over the next few years they will be able to improve the technique to make ALL immunotherapy even safer and more effective.
Article by S. Ghorashian et al. Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR is published in the journal Nature Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on UCL materials: New CAR T-cell therapy for leukaemia associated with fewer harmful side effects.