A new treatment developed by scientists at University College London (UCL) and Great Ormond Street Hospital (GOSH) has shown potential in treating T-cell acute lymphoblastic leukemia (T-ALL), a rare and aggressive blood cancer. The therapy, known as BE-CAR7, uses genome-edited immune cells that have undergone base-editing—a precise method for altering DNA using CRISPR technology.
In 2022, the first patient to receive this treatment was Alyssa Tapley, then 13 years old, from Leicester. Since then, eight more children and two adults have received the therapy at GOSH and King's College Hospital. Results from the clinical trial were published in the New England Journal of Medicine and presented at the American Society of Hematology Annual Meeting.
CAR-T cell immunotherapy involves modifying T-cells to express chimeric antigen receptors (CARs), which allow them to target specific markers on cancer cells. However, adapting this approach for T-cell leukemias has been challenging because the cancer originates from T-cells themselves.
BE-CAR7 T-cells are created through base editing, which avoids cutting DNA and lowers the risk of chromosomal damage. Researchers used chemical reactions guided by CRISPR to alter single DNA letters in healthy donor white blood cells. These edited cells can be stored and later administered to patients to seek out and destroy leukemic T-cells.
After receiving base-edited CAR-T cells, patients undergo bone marrow transplants if their leukemia is cleared within four weeks. The transplant helps rebuild their immune systems over several months.
Professor Waseem Qasim of UCL and GOSH led the research team. He stated: "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+ leukemia." He also noted: "Many teams were involved across the hospital and university and everyone is delighted for patients clearing their disease, but at the same time, deeply mindful that outcomes were not as hoped for some children. These are intense and difficult treatments - patients and families have been generous in recognising the importance of learning as much as possible from each experience."
Dr Deborah Yallop, consultant haematologist at King's College Hospital, commented: "We've seen impressive responses in clearing leukemia that seemed incurable – it's a very powerful approach."
The trial was sponsored by GOSH with support from several organizations including the Medical Research Council, Wellcome Trust, National Institute for Health and Care Research (NIHR), and Great Ormond Street Hospital Charity (GOSH Charity). Patients eligible under NHS care may inquire about participating through their healthcare providers.
GOSH Charity provided early funding for Professor Qasim's work on gene therapies and has committed over £2 million to extend access to BE-CAR7 therapy for ten more patients as part of an expanded cohort study. This initiative supports GOSH Charity’s campaign to build a new Children's Cancer Centre aimed at advancing pediatric oncology research.
Alyssa Tapley reflected on her experience: "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. I've done all those things that you're supposed to do when you're a teenager.
"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 manufacturing process for BE-CAR7 cells takes place at GOSH’s clean room facility using custom RNA technologies developed by UCL-GOSH researchers over several years. The team now operates out of the Zayed Centre for Research into Rare Disease in Children—a partnership between UCL and GOSH—supported by philanthropic contributions such as a £60 million gift from Her Highness Sheikha Fatima bint Mubarak in 2014.
The researchers expressed gratitude towards Anthony Nolan charity volunteers who donated blood or stem cells as well as participating families.
