October 08, 2014
3 min read

Modified gene therapy shows promise in SCID-X1

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

A majority of boys with X-linked severe combined immunodeficiency experienced T-cell recovery and infection clearance after undergoing gene therapy with a self-inactivating gamma-retrovirus vector, according to study results.

Salima Hacein-Bey-Abina, PharmD, PhD, of the department of biotherapy at Hôpital Necker – Enfants Malades in Paris, and colleagues sought to modify a Moloney murine leukemia virus-based gamma-retrovirus vector that expressed interleukin-2 receptor gamma-chain complementary DNA.

In a previous analysis, the retrovirus effectively restored immunity in patients with X-linked severe combined immunodeficiency (SCID-X1); however, a quarter of patients developed vector-induced leukemia.

Hacein-Bey-Abina and colleagues thus evaluated a modified, self-inactivating gamma-retrovirus vector in nine boys with SCID-X1. The boys received an infusion of autologous bone marrow–derived CD34+ cells transduced with the self-inactivating gamma-retrovirus vector. Median age at the time of infusion was 8 months.

Eight patients were alive at a median follow-up of 29.1 months (range, 12.1 to 38.7). One patient died 4 months after infusion due to a preexisting adenovirus infection.

One patient had no evidence of gene marking after treatment and underwent an umbilical-cord–blood transplant. The remaining seven patients exhibited gene marking in T cells and their T-cell proliferation returned to the normal range, leading to infection resolution. Six of these patients also had CD3+, CD4+ and CD8+ T-cell recovery.

Researchers noted the T-cell reconstitution demonstrated in this analysis was similar to the previous gamma-retrovirus vector results 6 months (P=.39) and 1 year (P=.28) after therapy.

No patients in the trial had developed leukemia by the time of the analysis.

“The self-inactivating gamma-retrovirus vector was compatible with high-titer vector production in a clinical setting, with good transduction efficiencies overall, leading to transgene expression that restored immunity in the majority of patients treated in this trial,” Hacein-Bey-Abina and colleagues wrote. “Specifically, we found that a modified gamma-retrovirus vector retained efficacy in the treatment of SCID-X1 through the generation of a functional polyclonal T-cell repertoire.”

Disclosure: See the study for a list of the researchers’ relevant financial disclosures.