Great Ormond Street Hospital (GOSH) is launching a clinical trial offering new hope for children with aggressive T-cell acute lymphoblastic leukemia (T-ALL). The trial utilizes CAR T-cell therapy targeting the CCR9 protein, a novel approach aimed at eradicating cancerous cells while preserving healthy T cells.
Targeting CCR9 in T-ALL
Unlike previous CAR T-cell therapies that have shown success in B-cell leukemias, T-ALL has remained a challenge. Researchers at GOSH and University College London Great Ormond Street Institute of Child Health have identified the protein CCR9 as a specific target present on cancerous T cells. This targeted approach aims to minimize the elimination of healthy T cells, reducing the need for subsequent bone marrow transplants.
Dr. Sara Ghorashian, a consultant haematologist at GOSH, explained that the CCR9 target is present on only a small proportion (1-2%) of total T cells. "This means that when we treat with CAR T-cell therapy, hopefully, we won’t be eliminating healthy T cells in any significant numbers," she stated. "This means that the patient’s leukemia will be eliminated if we’re lucky, but the patient’s healthy T cells will remain and will be able to continue fighting infection."
Trial Design and Innovation
The study will recruit 12 children with relapsed or resistant T-ALL who have not responded to conventional treatments like chemotherapy and bone marrow transplant. The CAR T-cell therapy, administered as an infusion, will be created at UCL. A significant aspect of this trial is its parallel design, running simultaneously for both children and adults. This innovative approach aims to address the historical lag in pediatric cancer research, where children often wait longer to access new therapies.
According to GOSH, only 12 anti-cancer medicines have been authorized for pediatric cancer specifically in the last decade, compared to over 150 for adult cancers. Dr. Ghorashian emphasized the need to test drugs in parallel for children, ensuring their safety and preventing delays in access to effective treatments.
The Great Ormond Street Hospital Charity has provided £2.4 million to support the study. Dr. Aoife Regan, GOSH Charity’s director of impact and charitable funding, highlighted the importance of this research in providing a potential new treatment option and laying the foundations for a more efficient clinical trial design.
Potential Benefits and Future Implications
Researchers believe this therapy holds promise, with preclinical studies demonstrating its ability to clear leukemia. Furthermore, children tend to tolerate CAR T-cell therapy better than adults, potentially leading to improved outcomes and reduced side effects compared to chemotherapy and bone marrow transplant.
Dr. Ghorashian hopes the trial will establish a precedent for future child-adult studies, advocating for the inclusion of children in clinical trials from the outset. "Our goal is to never have a situation where children are left behind and we hope that we can prove the benefit of this novel approach to influence a change in the law in the future," she said.
