SCID gene therapy normalizes immune system in affected infants

  • Mamcarz E & al.
  • N Engl J Med
  • 18 Apr 2019

  • International Clinical Digest
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.

Takeaway

  • 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.

Key results

  • 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.

Study design

  • 8 infants included; median age, 3.5 months.
  • Funding: American Lebanese Syrian Associated Charities; US state, federal grants.

Limitations

  • Small sample size.

Please confirm your acceptance

To gain full access to GPnotebook please confirm:

By submitting here you confirm that you have accepted Terms of Use and Privacy Policy of GPnotebook.

Submit