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Updated: Jan 9, 2026
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Generation of Human Chimeric Antigen Receptor Regulatory T Cells
Published on: January 3, 2025
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Gene-corrected regulatory T cell therapy for IL2RA deficiency.
Alvin S Ha1, Nechama Kalter2, Michael Rosenberg2
1Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
Molecular Therapy : the Journal of the American Society of Gene Therapy
|December 11, 2025
Summary
Gene-corrected regulatory T cells (Tregs) offer a potential new therapy for IL2RA deficiency, a rare autoimmune disease. This approach uses CRISPR-Cas9 to fix gene mutations, creating functional Tregs for a safer treatment than current options.
Area of Science:
- Immunology
- Gene Therapy
- Cell Therapy
Background:
- Bi-allelic germline deficiency of IL2RA causes a rare autoimmune condition characterized by impaired regulatory T cell (Treg) function and interleukin-2 (IL-2) signaling.
- Current definitive treatment, allogeneic hematopoietic stem cell transplantation, involves significant risks.
Purpose of the Study:
- To develop a novel therapeutic approach for IL2RA deficiency using ex vivo gene-corrected autologous Tregs (gcTregs).
- To establish a Good Manufacturing Practice (GMP)-compatible manufacturing process for personalized gcTreg therapies.
Main Methods:
- CRISPR-Cas9-mediated homology-directed repair was used to correct one of two disease-causing mutations in patient-derived Tregs.
- Gene correction aimed to restore IL2RA expression and Treg function.
- Clinical-scale manufacturing processes were developed and validated.
Main Results:
- The gcTregs demonstrated restored IL2RA expression and robust in vitro suppressive activity.
- Clinical-scale manufacturing achieved efficient gene correction and functional equivalence to healthy donor Tregs.
- The process was shown to be GMP-compatible.
Conclusions:
- Personalized gcTreg therapy represents a potentially safer treatment for IL2RA deficiency compared to current options.
- This approach provides a framework for treating other inborn errors of immunity involving Treg dysfunction.
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