Modified gene therapy shows promise in SCID-X1
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.