Immunotherapy of leukemia relapses
There are effective treatments for acute myeloid leukemia (AML), but the disease often recurs in patients even after achieving complete remission. A preclinical study conducted by researchers at Weill Medical College of Cornell University on animal models of AML has shown the effectiveness of a new therapy aimed at cancer cells responsible for the recurrence of the disease.
The researchers used CAR T therapy, in which T lymphocytes are modified to produce chimeric antigen receptors (CAR) to recognize specific markers on cancer cells. In this study, CAR is a receptor that binds to the CD123 molecule on leukemia stem cells, allowing altered T cells (UCART123) to seek and attack them.
Stem leukemia cells are a subset of cancer cells that are resistant to standard chemotherapy drugs and can cause disease recurrence; CD123 is a marker found on stem leukemia cells.
UCART123 cells have several very important features: they target the marker of leukemia stem cells, are obtained from healthy donors and are manufactured so as to be ready for use at any time when it is necessary. In addition, they are specially designed in such a way as to minimize toxic side effects, and in the case of excessive proliferation, they can be eliminated with a drug called rituximab.
The researchers tested UCART123 on a mouse model of AML and found that the therapy effectively eliminates leukemia cells and increases survival. They also developed an ultra-sensitive monitoring strategy to detect any residual cancer cells and assess resistance to UCART123 cells. Finally, the group demonstrated that UCART123 cells have specificity against leukemia cells – with minimal toxicity to normal animal blood cells.
The success of preclinical trials led UCART123 to a phase 1 clinical trial involving patients with recurrent or unresponsive AML therapy.
Article by M.Sugita et al. Allogeneic TCRaß deficient CAR T-cells targeting CD123 in acute myeloid leukemia is published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Weill Cornell Medicine: Immune Therapy Targets Cells that Cause Leukemia Relapse.