March 31, 2025
RECOMB Project: Advancing Gene Therapy for RAG1-SCID
On March 10, 2025, the RECOMB project—funded by Horizon 2020 and concluded on Dec 31, 2024—successfully had its final review meeting. This collaborative initiative aimed to develop a curative treatment for RAG1-SCID, a severe combined immune deficiency caused by a mutation in the RAG1 gene. This mutation prevents the proper development of T cells in the thymus and B cells in the bone marrow, leaving infants highly vulnerable to infections. The project’s goal was to demonstrate that lentiviral gene therapy could safely correct patient cells and cure this life-threatening condition.
So far, the clinical trial has included 17 patient consultations, with 5 patients included in the trial. Encouragingly, all treated patients have shown signs of recovery, and the first two patients are far enough after treatment to show antibody responses to vaccines, immune system restoration, and no longer requiring immunoglobulin replacement therapy. These promising results highlight the potential of gene therapy to cure fatal immune disorders and further strengthen Europe’s expertise in this field.
A key principle of the project—“Cells travel, not the patient/family”—was successfully implemented. This approach allowed families to access life-saving treatment in multiple regions, including outside Europe, without the burden of extensive travel with fragile infants. These established protocols will help future RAG1-SCID patients receive treatment more easily as the clinical trial progresses.
The consortium also developed standardised immune-monitoring protocols that can be applied to other conditions. Additionally, new safety tests were created to assess retroviral vectors used in gene therapy. The team remains committed to improving the safety of these vectors while continuing to monitor treated patients.
Lastly, a cost-benefit analysis confirmed that gene therapy could be a cost-effective solution for SCID patients by significantly increasing life expectancy. This finding supports future investment in and approval of gene therapies. Although the RECOMB project has officially ended, the consortium remains dedicated to ongoing patient follow-ups and recruiting new patients as the therapy moves through the complex process of market approval.
Acknowledgment: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 755170.
