- 8 infants with X-linked severe combined immunodeficiency syndrome (SCID-X1) treated with lentiviral vector gene therapy and low-exposure busulfan experienced considerable immune system normalization.
- This trial of gene therapy produced multilineage cell engraftment, along with IgM and T-cell normalization.
Why this matters
- Allogeneic approaches have limited success, and autologous gene therapy with some viral vectors has had partial success but with leukemia as a complication.
- This lentiviral vector-based therapy has been effective in some older patients (age, 7-23 years) with SCID-X1.
- Authors: the hope is for “durable, complete adaptive immunity” to be established in these patients.
- Follow-up: median 16.4 months.
- In 7 of 8 infants:
- T cells (CD3+, CD4+, naive CD4+), natural killer (NK) cells normalized by age 3-4 months; IgM normalized.
- Vector marking detected in T and B cells, NKs, myeloid cells, bone marrow progenitor cells.
- 4 of these 7 could discontinue intravenous Ig; 3 of these 4 had vaccine response, too.
- 1 infant had a delayed response but eventually experienced similar results.
- All infants had clearance of previous infections.
- Busulfan-related adverse events resolved.
- 8 infants included; median age, 3.5 months.
- Funding: American Lebanese Syrian Associated Charities; US state, federal grants.
- Small sample size.