Innovative therapy gives hope to patients whose blood cancer ‘seemed incurable’
Almost two thirds of patients with T-cell acute lymphoblastic leukaemia involved in a clinical trial of the treatment are now disease-free.
A pioneering treatment that edits healthy immune cells to fight cancer has shown promise for adults and children with a rare and aggressive form of leukaemia that “seemed incurable”.
Almost two thirds of patients with T-cell acute lymphoblastic leukaemia (T-ALL) involved in a clinical trial of the treatment – known as BE-CAR7 – now remain disease-free.
BE-CAR7 was developed by scientists at Great Ormond Street Hospital (Gosh) and University College London (UCL).
It is a highly advanced version of an immunotherapy known as CAR T-cell treatments.
CAR T-cell therapy typically involves a doctor collecting T cells from a patient.
They are then modified in a lab, with proteins called chimeric antigen receptors (CARs) placed on the surface to recognise and kill cancer.
The immune cells are then placed back into the patient’s bloodstream using a drip.
However, developing CAR T-cell therapy for leukaemia which has developed from abnormal T cells has been challenging.
BE-CAR7 uses healthy T cells from a donor to create an “off-the-shelf” version of this treatment.
This new process of tweaking T cells is called base editing, and allows them to work after chemotherapy, as well as disarming them to prevent attacks against normal cells.
Base-editing is an advanced version of the gene-editing tool Crispr, which earned its inventors the Nobel Prize for chemistry in 2020, and can change single letters of DNA code inside living cells.
A clinical trial explored whether BE-CAR7 could clear leukaemia ahead of a planned bone marrow transplant in the hopes it could stop the cancer returning.
Nine children and two adults with T-ALL were treated as part of the study at Gosh and King’s College Hospital.
Now, some 64% remain disease-free, with the first patients off treatment three years on.
More than eight in 10 (82%) achieved deep remission and were able to get a stem cell transplant without disease.
Side effects, including low blood count and rashes, were tolerable, according to researchers.
Waseem Qasim, a professor of cell and gene therapy at UCL and honorary consultant immunologist at Gosh, said: “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.
“We’ve shown that universal or ‘off-the-shelf’ base-edited CAR T-cells can seek and destroy very resistant cases of CD7+ leukaemia.”
Dr Rob Chiesa, study investigator and bone marrow transplant consultant at Gosh, said: “Although most children with T-cell leukaemia will respond well to standard treatments, around 20% may not.
“It’s these patients who desperately need better options and this research provides hope for a better prognosis for everyone diagnosed with this rare but aggressive form of blood cancer.”
BE-CAR7 was first administered to Alyssa Tapley, then 13, from Leicester in 2022.
She was diagnosed with T-cell leukaemia in May 2021 and did not respond to standard therapies.
Alyssa, who is now 16, said: “I chose to take part in the research as I felt that, even if it didn’t work for me, it could help others.
“Years later, we know it worked and I’m doing really well.”
Dr Deborah Yallop, consultant haematologist at King’s College Hospital, said “We’ve seen impressive responses in clearing leukaemia that seemed incurable – it’s a very powerful approach.”
Alyssa now has hopes of becoming a research scientist.
“I’ve done all those things that you’re supposed to do when you’re a teenager,” she said.
“I’ve gone sailing, spent time away from home doing my Duke of Edinburgh Award, but even just going to school is something I dreamed of when I was ill.
“I’m not taking anything for granted.
“Next on my list is learning to drive, but my ultimate goal is to become a research scientist and be part of the next big discovery that can help people like me.”
The results of the clinical trial have been published in the New England Journal of Medicine and presented at the 67th American Society of Hematology Annual Meeting in Florida.
Reacting to the findings, Dr Tania Dexter, senior medical officer at stem cell charity Anthony Nolan, said: “The results of the study are promising, with most patients achieving levels of remission allowing them to receive a stem cell transplant.
“Considering these patients had a low chance of survival before the trial, these results bring hope that treatments like this will continue to advance and become available to more patients.
“As with any novel cellular therapy, this phase 1 trial is just an initial indication of the effectiveness and safety of the treatment, and more work must be done to determine its wider clinical application.
“Yet the results are encouraging and demonstrate the recent leaps in technology that are allowing us to take on even greater challenges in the treatment of blood cancers and blood disorders.”
