A first-in-class clinical trial has supported the feasibility of using “ready-made” CAR T cells to fight T-cell acute lymphoblastic leukemia (ALL).
The Phase I study is a step towards using this form of immunotherapy to move patients into remission if leukemia has returned or not responded following chemotherapy, so they can receive a bone marrow transplant.
The findings are reported in the New England Journal of Medicine and are also being presented this week at the American Society of Hematology annual meeting in Orlando, Florida.
These ‘ready-made’ CAR T cells are produced by base editing donor T cells, removing existing receptors to create universal cells that don’t require matching to recipients.
Next-generation genome editing precisely modifies their DNA, with the resulting cells targeting the CD7 T-cell marker that has consistently high and stable expression in T-cell ALL blast populations.
The treatment involves CRISPR C to T base editing to generate BE-CAR7 T cells, using a technique that was first delivered to a 13-year-old girl in the U.K. in 2022. Another eight children and two adults have now undergone treatment.
“We previously showed promising results using precision genome editing for children with aggressive blood cancer and this larger number of patients confirms the impact of this type of treatment,” said lead researcher Waseem Qasim, PhD, from University College London.
“We’ve shown that universal or ‘off the shelf’ base-edited CAR T cells can seek and destroy very resistant cases of CD7+ leukemia.”
The technique involves removing CD7 and CD52 flags on the cells, which means they are no longer identifiable as T cells and can evade antibody drugs given to suppress a patient’s immune system.
A chimeric antigen receptor (CAR) is then added that recognizes the CD7 marker on leukemic T cells.
Results showed that 82% of patients achieved very deep remissions at four weeks after a single infusion of BE-CAR7 cells, enabling these participants to proceed to stem cell transplantation, which eliminated remaining BE-CAR7 cells.
Two patients with quantifiable minimal residual disease in bone marrow received palliative care.
Overall, seven of the 11 patients (64%) were in ongoing remission, with the first patients remaining disease-free and off treatment three years later.
Side effects including low blood counts, cytokine release syndrome and rashes were tolerable, with the greatest risks from virus infections until the recovery of immunity. Viral reactivations were frequent, with three patients having clinically significant virus-related complications after transplantation.
“In this Phase I study, we found that universal BE-CAR7 T cells induced antileukemic responses in all the patients with relapsed or refractory CD7+ T-cell ALL who received the treatment, which enabled nine patients to undergo allogeneic hematopoietic stem-cell transplantation in deep remission,” the researchers concluded.
“Limitations included CD7 antigen loss and risks of viral-related complications.”
