Credit: Chad McNeeley
A new gene therapy appears safe and effective for boys with X-linked severe combined immunodeficiency syndrome (SCID-X1).
Early data from a small trial suggest the treatment may not pose a risk of leukemia, which was seen in previous trials of gene therapy in SCID-X1 patients.
The new therapy is a self-inactivating γ-retrovirus designed to deliver its payload while minimizing the chance of inadvertently activating
oncogenes that could lead to leukemia.
Researchers described results with this therapy in The New England Journal of Medicine.
The team enrolled 9 boys with SCID-X1. They received bone marrow-derived CD34+ cells transduced with the self-inactivating γ-chain vector, without preparative conditioning.
Eight boys are still alive after 12.1 to 38.7 months of follow-up, with no SCID-X1-associated infections. One child died of an overwhelming infection that was present at the time gene therapy began.
Gene therapy alone generated functioning immune systems in 7 of the patients.
Genetic studies of the boys’ new T cells revealed that the viral vector did not lead to an expansion of cells with vector insertions near known oncogenes, raising cautious hopes about the vector’s long-term safety.
The researchers said they will continue to monitor the patients for any signs of treatment-related leukemia for 15 years.
In prior European trials, which were the first to demonstrate gene therapy’s potential to successfully cure a disease, leukemia appeared 2 to 5 years after treatment. This outcome was one of several events that, together, slowed clinical progress in gene therapy for many years.
“Our goal was to take the molecular data from the prior trial and use it to produce a vector that would remain effective and, at the same time, reduce the risk of leukemia,” said David A. Williams, MD, of the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Massachusetts.
“The efficacy data from our study is clear: The vector does work to correct the disease. And by a surrogate endpoint, we have improved the treatment’s safety, although it’s too early to say that we’ve completely eliminated the long-term risk of leukemia.”
After a single round of treatment, 6 of 7 boys for whom the gene therapy was successful had achieved the trial’s primary efficacy endpoints—a T-cell count greater than 300 cells per microliter of blood and T-cell proliferation in response to stimulation with phytohemagglutinin.
The seventh boy received a second round of gene therapy and remains healthy despite having relatively low T-cell counts. The eighth surviving patient was successfully treated with a conventional hematopoietic stem cell transplant after gene therapy failed to stimulate T-cell production.
