“In vivo gene therapy could be a true game changer for the field”
At the 52nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) in Madrid, Prof Claire Booth (University College London and Great Ormond Street Hospital, London, UK) presented a plenary session on gene therapy in primary immunodeficiencies – a field that is rapidly shifting from experimental promise to clinical reality. In this interview, she reflects on the field’s most important milestones, how gene therapy compares with allogeneic transplantation, and the critical challenge of ensuring patients can actually access these transformative treatments.
There’s lots to talk about there.
Over the past 30 years, primary immunodeficiencies have really served as the test bed for modern gene therapy. What’s been particularly striking in the last two to three years is the emergence of robust evidence for the long-term safety and durability of ex vivo lentiviral stem cell therapies. We’re now seeing consistent results across multiple diseases, trials and centres. That’s hugely important – it tells us not only that the approach works, but that it works sustainably over time.
There have been remarkable advances even in just the past couple of years. We now have more active lentiviral gene therapy trials in immunodeficiencies than ever before, and we’re targeting the widest range of diseases to date. Importantly, first-in-human studies are still emerging.
At the same time, newer technologies are entering the clinic. Base editing and prime editing are now being applied in patients, with pioneering work from the NIH. We’ve also seen the first patient treated with in vivo stem cell – targeted gene therapy for chronic granulomatous disease – an extraordinary step forward.
And crucially, we’ve reached a regulatory milestone: the Telethon Foundation has brought a gene therapy for Wiskott–Aldrich syndrome to market. That represents a major achievement for the field.
Gene therapy has several inherent advantages. Because we use the patient’s own cells, there’s no risk of graft-versus-host disease or alloimmune complications. We can also use less intensive conditioning and avoid long-term immunosuppression, making it a potentially safer and less toxic option.
While transplantation has a longer track record, gene therapy outcomes are becoming increasingly comparable. In fact, emerging data suggest superiority in certain areas. For example, in a recent multicentre SCID trial, we observed better T-cell reconstitution compared with both allogeneic transplant and earlier gene therapy approaches. That said, long-term data are still evolving, and we need continued follow-up.
This is one of the biggest challenges we face, in the rare disease field, not just immune deficiency. Even when therapies reach approval (for example betibeglogene autotemcel and elivaldogene autotemcel in Europe) they don’t always remain available – largely because the patient populations are so small that commercial models struggle to sustain them.
For some conditions, we’re talking about treating perhaps ten patients per year across Europe. That’s simply not commercially viable. As a result, we’re seeing therapies withdrawn from certain markets despite clear clinical benefit.
There is progress, though. We’re exploring alternative delivery models, including not-for-profit approaches within healthcare systems like the NHS. Regulatory innovation, such as platform approvals, may also help. But fundamentally, access remains a major hurdle.
It’s a nuanced decision. Gene therapy may be particularly advantageous for older patients with comorbidities that increase transplant risk. At the same time, newborn screening for conditions like SCID is identifying patients earlier, opening the door to early intervention with gene therapy – which could improve outcomes and reduce long-term healthcare burden.
In vivo gene therapy is the development I’m most excited about. Currently, ex vivo approaches are complex and resource-intensive – we have to remove, modify and reinfuse stem cells.
If we can deliver gene therapy directly into the body and target stem cells in situ, we could dramatically simplify the process and expand access. We’ve already seen the first patient treated this way, and if the results are positive, it could truly be a game changer.
About the European Society for Blood and Marrow Transplantation (EBMT)
The EBMT is a community of healthcare professionals, involved in clinical haematopoietic cell transplantation and cellular therapy, who share their experiences and develop co-operative studies. The EBMT has a governing body called the Board of Association and three sets of groups that channel the society’s research aims and other activities: the EBMT Working Parties, Committees, and Nurses Group, which addresses issues within the field specifically related to nursing.
This content has been developed in collaboration with the European Society for Blood and Marrow Transplantation for touchHEMATOLOGY. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Cite: EBMT 2026: Advancing gene therapy in primary immunodeficiencies. touchHEMATOLOGY. 15th April 2026.
Interviewer: Caroline Markham
Disclosures: Claire Booth is a consultant for Ensoma (ad hoc) and has received educational honoraria/honorarium from Chiesi, Grifols.
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