World-First Base-Edited CAR-T Therapy Shows 64% Disease-Free Survival in Previously Untreatable T-Cell Leukemia
核心洞察
A groundbreaking base-edited CAR-T cell therapy called BE-CAR7 (搜索) achieved 82% deep remission rates in patients with previously untreatable T-cell acute lymphoblastic leukemia (搜索).
Clinical trial results published in the New England Journal of Medicine show 64% of patients remain disease-free, with some now three years post-treatment.
The therapy uses advanced base-editing technology to create "universal" donor T-cells (搜索) that can target and destroy leukemic T-cells without requiring patient matching.
Patients with a previously untreatable form of blood cancer (搜索) are now living disease-free after receiving a world-first gene therapy that uses base-edited immune cells to target T-cell acute lymphoblastic leukemia (搜索) (T-ALL (搜索)). Results from a clinical trial involving 11 patients at Great Ormond Street Hospital (搜索) (GOSH) and King's College Hospital show that 64% remain disease-free, with some patients now three years post-treatment.
The breakthrough therapy, called BE-CAR7 (搜索), represents a significant advance in treating this rare and aggressive form of blood cancer (搜索) that affects approximately 20% of T-cell leukemia (搜索) patients who fail to respond to standard treatments. According to results published in the New England Journal of Medicine, 82% of patients achieved very deep remissions after treatment, enabling them to proceed to stem cell transplant without detectable disease.
Revolutionary Base-Editing Technology
BE-CAR7 (搜索) uses base-editing, an advanced version of CRISPR technology that can precisely change single letters of DNA code inside living cells without cutting the DNA, reducing the risk of chromosomal damage. The therapy creates "universal" CAR-T cells (搜索) from healthy donor white blood cells through a complex four-step engineering process conducted in clean room facilities at GOSH.
Professor Waseem Qasim, who led the research and is professor of cell and gene therapy at UCL, explained: "We've shown that universal or 'off the shelf' base-edited CAR T-cells (搜索) can seek and destroy very resistant cases of CD7 (搜索)+ leukaemia." The engineering process involves removing existing receptors to make the cells universal, eliminating CD7 and CD52 (搜索) markers, and adding a chimeric antigen receptor that recognizes leukemic T-cells.
Clinical Trial Results and Patient Outcomes
The study included eight children and two adults who had all failed to respond to existing treatments. When administered, the base-edited CAR-T cells (搜索) rapidly find and destroy all T-cells (搜索) in the body, including leukemic cells. If the leukemia (搜索) is eradicated within four weeks, patients can proceed to bone marrow transplant to rebuild their immune system.
Dr. Deborah Yallop, consultant haematologist at King's College Hospital, noted: "We've seen impressive responses in clearing leukaemia that seemed incurable - it's a very powerful approach." The treatment showed tolerable side effects including low blood counts, cytokine release syndrome, and rashes, with the greatest risks arising from viral infections until immunity recovered.
First Patient Success Story
Alyssa Tapley, now 16, became the first patient worldwide to receive base-edited cell therapy in 2022 when she was 13 years old. After failing to respond to chemotherapy and a first bone marrow transplant, she was considering palliative care options before enrolling in the trial.
"I chose to take part in the research as I felt that, even if it didn't work for me, it could help others," Alyssa said. "Years later, we know it worked and I'm doing really well. 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."
Future Treatment Expansion
Dr. Rob Chiesa, study investigator and bone marrow transplant consultant at GOSH, emphasized the significance for patients who don't respond to standard treatments: "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 (搜索)."
Great Ormond Street Hospital (搜索) Charity has committed over £2 million to support treatment for an additional 10 patients as part of an extended trial cohort. The funding supports the charity's ongoing appeal to build a world-leading Children's Cancer Centre at GOSH.
Research Collaboration and Support
The trial was sponsored by GOSH and supported by the Medical Research Council, Wellcome, and the National Institute for Health and Care Research (NIHR). The research team collaborated with UK stem cell charity Anthony Nolan (搜索), which provided T-cell donors for the study.
Dr. Tania Dexter, senior medical officer at Anthony Nolan (搜索), commented: "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." She noted that while this phase 1 trial provides initial indication of effectiveness and safety, more work is needed to determine wider clinical application.