A collaborative research initiative between UCL, Great Ormond Street Hospital, and the Wellcome Sanger Institute has unveiled new insights into the long-lasting efficacy of CAR T-cell therapy in treating childhood leukemia. Through a cutting-edge combination of immune therapy design and computational analysis, the researchers have identified a genetic signature within CAR T-cells that predicts long-term effectiveness.
In recent times, these genetically modified T-cells, designed to target a specific type of leukemia called B-cell acute lymphoblastic leukemia (B ALL), have emerged as a key treatment for children with recurrent or incurable forms of the disease.
The persistence of CAR T-cells in the body is a vital factor in achieving long-term remission. The research team, working for years with families post-treatment in a study called CARPALL, has begun to understand why some CAR T-cells persist while others do not. Through the use of advanced single-cell genomics, they have identified the code of persistence in these cells for the first time.
The researchers were able to examine CAR T-cells from 10 children up to five years after treatment. They discovered a unique signature in cells that lasted long, allowing them to continue guarding the patient’s body against cancer cells. This signature was also found in adult patients with a different type of leukemia, indicating its universal importance in CAR T-cell persistence.
A focus of the study was the identification of key genes that allow CAR T-cells to remain in the body, providing essential data for future research to enhance the effectiveness of these treatments.
The success of this research owes much to the dedication of the children and their families who participated in the study, continuing to contribute cell samples up to five years after initial treatment. Their involvement has provided the researchers with invaluable insights into new therapies, paving the way for improved treatments in the future.
Dr. Nathaniel Anderson, lead author from the Wellcome Sanger Institute, emphasized that the study marks the first major step in understanding why certain CAR T-cells endure, and this work will aid in refining an already transformative treatment. Other senior authors expressed gratitude to the families involved and highlighted the study’s importance in the global effort to enhance leukemia treatments.
Supporting the continued advancement of immunotherapies like CAR T-cell therapy, this research brings the medical community a step closer to tailoring these therapies for increased effectiveness across a broader range of cancer patients.
The study was part-funded by Cancer Research UK and supported by various institutions and funding schemes, including the CRUK/AIRC Accelerator Award Scheme for the INCAR consortium, Wellcome, Marie Sklodowska-Curie Actions, and the Olivia Hodson Cancer Fund, among others. The original CARPALL study also received support from multiple children’s charities and research institutes.
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Frequently Asked Questions (FAQs) about CAR T-cell therapy
What is the main discovery of the research conducted by UCL, Great Ormond Street Hospital, and the Wellcome Sanger Institute?
The research identified a genetic signature in CAR T-cells, which indicates long-term effectiveness in treating childhood leukemia. This discovery offers a pathway to optimizing treatments and enhancing long-term remission outcomes.
Who were the participants in this research?
The research involved collaboration between scientists from UCL, Great Ormond Street Hospital, and the Wellcome Sanger Institute, along with families of children who received CAR T-cell treatment for leukemia.
How might this discovery impact future leukemia treatments?
The identification of the genetic signature in CAR T-cells will likely enable clinical teams and manufacturers to better understand which patients will respond best to treatments. It will also help in optimizing methods for maintaining CAR T-cell persistence, leading to improved outcomes for patients.
What was the role of the children and families in this study?
Children and their families who had undergone CAR T-cell therapy contributed by donating cells for up to five years after treatment. Their continued involvement provided invaluable insights into the long-term persistence of these cells, aiding in the advancement of this cutting-edge therapy.
How were the CAR T-cells studied and what techniques were used?
The researchers studied CAR T-cells from 10 children for up to five years after treatment. They used advanced techniques such as single-cell genomics to analyze individual cells at a genetic level. This allowed them to identify a unique signature in long-lasting CAR T-cells, which is essential for extended remission in children.
What types of leukemia were treated with CAR T-cell therapy in this research?
The study focused on CAR T-cell therapy for treating a specific type of leukemia called B-cell acute lymphoblastic leukemia (B ALL), both in children with relapsed or incurable forms of the disease and in adults treated with a different CAR T-cell product for a different type of leukemia.
Who funded and supported this research?
The research was part-funded by Cancer Research UK and supported by a range of institutions and schemes, including the CRUK/AIRC Accelerator Award Scheme for the INCAR consortium, Wellcome, Marie Sklodowska-Curie Actions, the Olivia Hodson Cancer Fund, Children with Cancer, GOSH Children’s Charity, and various research institutes.
More about CAR T-cell therapy
- Nature Medicine
- Wellcome Sanger Institute
- Great Ormond Street Hospital
- UCL Great Ormond Street Institute of Child Health
- Cancer Research UK
