This first-of-its-kind gene therapy, known as BE-CAR7, relies on base-edited immune cells to attack types of T-cell leukemia that historically could not be treated effectively. Base-editing is an advanced form of CRISPR that changes individual DNA letters inside living cells with high precision.

In 2022, researchers at GOSH and UCL used this technology to treat Alyssa, a 13-year-old girl from Leicester, marking the first time a base-edited therapy had been used in a patient anywhere in the world.

Since then, the treatment has been given to eight more children and two adults at GOSH and King's College Hospital (KCH).

Clinical trial results show strong remission rates

Findings from the early clinical trial have been published in the New England Journal of Medicine and shared at the 67th American Society of Hematology Annual Meeting. Key outcomes reported by the research team include:

• 82% of patients reached very deep remission after receiving BE-CAR7, which allowed them to move forward to a stem cell transplant without detectable disease
• 64% remain free of leukemia, and the earliest treated patients have now been disease-free and off therapy for three years
• Side effects such as low blood counts, cytokine release syndrome and rashes were expected and manageable, although the highest risks were linked to viral infections while the immune system was rebuilding

How CAR T-cell therapy works

CAR-T cell immunotherapy has become an important option for several blood cancers. The process modifies a patient's T-cells so they carry a customized protein called a chimeric antigen receptor (CAR). This receptor helps the modified cell identify unique markers or "flags" on cancer cells and destroy them.

Developing CAR T-cell therapies for leukemias that originate in T-cells has been especially difficult. The challenge is that the treatment must wipe out cancerous T-cells without triggering the engineered cells to attack one another.

Base-editing enables the creation of universal CAR T-cells

BE-CAR7 T-cells are created with a next-generation genome editing method that does not cut DNA, which lowers the chances of chromosomal damage. Using CRISPR-based tools, researchers altered single DNA letters to reprogram the cells. In 2022, these edits allowed the team to produce banked stores of "universal" CAR T-cells that can be delivered to different patients and still recognize and attack T-cell leukemia.

For this study, the universal CAR T-cells came from the white blood cells of healthy donors. The engineering steps took place in a clean room facility at GOSH using custom RNA, mRNA and a lentiviral vector in an automated system the team previously refined. Key steps included:

• Removing existing receptors so donor cells can be stored and given to any patient without the need for a match, creating "universal" T-cells
• Removing the CD7 marker that identifies cells as T-cells (CD7 T-cell marker). Without removing CD7, T-cells designed to kill T-cells would destroy one another in "friendly-fire"
• Removing CD52, a second marker. This alteration prevents a strong antibody medication used to suppress the immune system from eliminating the engineered cells
• Adding a Chimeric Antigen Receptor (CAR) that detects CD7 on leukemic T-cells. A disabled virus provided extra DNA instructions so the cells can find and attack CD7-positive leukemia

From cancer clearance to immune rebuilding

When patients receive base-edited CAR T-cells, the engineered cells quickly locate and destroy T-cells throughout the body, including the cancerous ones. If leukemia is cleared within the first month, patients then undergo a bone marrow transplant that restores a functioning immune system over the following months.

Professor Waseem Qasim, who led the research and is 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+ leukemia."

He added: "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 recognizing the importance of learning as much as possible from each experience."

New hope for patients who do not respond to standard therapy

Dr. Rob Chiesa, a study investigator and bone marrow transplant consultant at GOSH, said: "Although most children with T-cell leukemia 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.

"Seeing Alyssa go from strength-to-strength is incredible and a testament to her tenacity and the dedication of an array of small army of people at GOSH. Team working between bone marrow transplant, hematology, ward staff, teachers, play workers, physiotherapists, lab and research teams, among others, is essential for supporting our patients."

Dr. Deborah Yallop, consultant hematologist at KCH, said: "We've seen impressive responses in clearing leukemia that seemed incurable -- it's a very powerful approach."

Funding expands access to more T-ALL patients

The trial is sponsored by GOSH and supported by the Medical Research Council, Wellcome and the National Institute for Health and Care Research (NIHR). Patients eligible for NHS care who are interested in taking part should speak with their healthcare team.

GOSH Charity has also committed funding to support treatment for an additional 10 T-ALL patients. This more than £2m investment helps broaden access to the trial and contributes to GOSH Charity's fundraising campaign for a new Children's Cancer Centre designed to advance cutting-edge research.

Alyssa's recovery continues to inspire progress

Alyssa Tapley, now 16, became the first person in the world to receive a base-edited cell therapy. She shared her story in 2022, when her leukemia was undetectable but she remained under careful monitoring. She has since moved to long-term follow-up and is fully engaged in daily life with her friends.

She was diagnosed with T-cell leukemia in May 2021 after months of what appeared to be repeated viral illnesses and fatigue. Standard treatments such as chemotherapy and a first bone marrow transplant did not work, and discussions about palliative care had begun when the research team offered the experimental therapy.

Alyssa 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. 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."

Research infrastructure and continued support

BE-CAR7 cells were manufactured through a long-term research program at the UCL Great Ormond Street Institute of Child Health, led by Professor Qasim, who also serves as an honorary consultant at GOSH. Support from NIHR, Wellcome, the Medical Research Council and GOSH Charity has helped drive the development of innovative genome editing treatments.

The team now operates from the Zayed Centre for Research into Rare Disease in Children, a partnership between UCL and GOSH made possible through a £60 million gift in 2014 from Her Highness Sheikha Fatima bint Mubarak in honor of her late husband, Sheikh Zayed bin Sultan Al Nahyan.

The researchers expressed their thanks to Anthony Nolan and to the volunteer blood and stem cell donors, as well as the patients and families who chose to take part in this work.

• Chronic hepatitis C infection affects an estimated 50 million people around the world and leads to approximately 242,000 deaths each year, most often from cirrhosis and liver cancer.
• Same-day test results can speed up the start of treatment, and the infection is fully curable with the right medication.
• Scientists at Johns Hopkins independently verified that the new test showed 100 percent agreement with commercial diagnostic platforms.

A New 15 Minute Test Speeds Up Hepatitis C Detection

Scientists at Northwestern University have created the fastest method so far for identifying hepatitis C virus (HCV). The new diagnostic delivers accurate results in only 15 minutes -- up to 75 percent faster than other rapid HCV options. This shorter wait time is important because it allows many patients to begin treatment before leaving their appointment, reducing the chance of severe complications and deaths linked to delayed care.

The research describing the test is scheduled for publication on Dec. 10 in The Journal of Infectious Diseases.

Why Faster Diagnosis Matters for Global Hepatitis C Control

HCV can progress to chronic hepatitis C infection, a condition that affects about 50 million people worldwide and leads to roughly 242,000 deaths each year. Most of these deaths result from cirrhosis and liver cancer. Although highly effective medications can cure the infection in 8 to 12 weeks, treatment rates remain low. One major barrier is limited access to affordable, easy to use diagnostic tools that can be deployed at the point of care.

"We were able to develop a diagnostic test that can be performed at the point of care during a patient's clinical visit, which could enable same-day diagnosis and treatment in support of HCV elimination efforts," said Sally McFall, co-director of the Center for Innovation in Global Health Technologies (CIGHT) at Northwestern University McCormick School of Engineering, who developed the test.

According to McFall, the new tool has shown strong analytical and clinical results. She noted that it may help support the World Health Organization's goal of eliminating HCV by 2030.

How the Rapid PCR Test Was Developed

The project brought together faculty in engineering and infectious disease at Northwestern. To build the new rapid polymerase chain reaction (PCR) test, the team relied on the DASH® (Diagnostic Analyzer for Specific Hybridization)PCR platform. Originally designed at Northwestern to detect COVID from nasal swabs, the system proved flexible enough to process whole blood samples for HCV detection.

To validate the technology, the researchers sent DASH® analyzers and DASH® HCV cartridges to colleagues at Johns Hopkins University. The Johns Hopkins team tested 97 clinical specimens and reported a 100 percent match between the DASH results and commercial diagnostic platforms.

"This test could revolutionize HCV care in the U.S. and globally by dramatically improving diagnosis, accelerating treatment uptake and enabling more people to be cured faster," said study co-author Dr. Claudia Hawkins, director of the Robert J. Havey, MD Institute for Global Health's Center for Global Communicable and Emerging Infectious Diseases at Northwestern. "By reducing delays and simplifying testing pathways, it has the potential to save millions of lives from the devastating liver-related complications of untreated HCV."

Why the New Test Outperforms Current Options

Diagnosing hepatitis C typically requires two steps. An antibody test first determines whether a patient has ever been exposed to the virus. If that test is positive, a follow-up PCR test checks for viral RNA to confirm an active infection. In most clinical settings, the PCR sample must be sent to an outside laboratory, leading to delays that can stretch from several days to weeks. Patients then need to return to their provider for results. Although the Food and Drug Administration has cleared one other point-of-care HCV test, it still requires 40 to 60 minutes -- a time frame that often exceeds the length of a standard appointment, McFall said.

The study is titled, "Development of a Rapid Automated Point-of-Care Test for Hepatitis C Viral RNA on the DASH(r) Rapid PCR System."