Research led by Naval Medical University’s Changzheng Hospital in China reports that an off-the-shelf cell therapy built from induced pluripotent stem cells (iPSCs) loosened life-limiting skin and organ scarring in a woman with systemic sclerosis.
Systemic sclerosis progressively suffocates tissue through immune misfires, collapsed micro-vessels, and runaway collagen conditions that resist standard immunosuppressants, biologics, and anti-fibrotic drugs while driving a 40% 10-year mortality.
Cell-based approaches such as hematopoietic-stem-cell transplants and CAR-T therapies have shown promise but carry high toxicity or labor-intensive custom manufacturing, leaving clinicians and patients in search of safer, more accessible tools.
In the study, “An iPSC-derived CD19/BCMA CAR-NK therapy in a patient with systemic sclerosis,” published in Cell, researchers engineered an allogeneic cell therapy, QN-139b, to deplete pathogenic B cells and restore tissue architecture.
Treatment was administered to a 36-year-old woman with severe diffuse cutaneous systemic sclerosis at Changzheng Hospital in Shanghai.
Researchers prepared QN-139b by genetically editing human induced pluripotent stem cells to knock out B2M, CIITA, and CD16, while inserting HLA-E, HLA-G, interleukin-2 receptor fusion (IL-2RF), truncated epidermal growth factor receptor (tEGFR), and bicistronic chimeric antigen receptors targeting CD19 and BCMA.
The modified cells were differentiated into natural killer lineage and expanded. Lymphodepletion was achieved with cyclophosphamide at 300 mg/m2 and fludarabine at 25 mg/m2 for three days. Four infusions of 6×108 QN-139b cells were given intravenously on days 0, 3, 7, and 10.
Peripheral B cell counts fell rapidly after infusion, with near-total depletion by day 7. Serum levels of antibodies declined steadily over six months. Skin fibrosis regressed, as shown by reductions in modified Rodnan Skin Score and improved ultrasound elastography. Nailfold capillaroscopy revealed restoration of capillary loops and reduced hemorrhagic infarcts.
High-resolution lung imaging demonstrated diminished ground-glass opacities and reticular patterns. Cardiac MRI showed decreased late gadolinium enhancement in the left ventricular lateral wall.
No cytokine-release syndrome, neurotoxicity, or graft-versus-host disease occurred.
Importantly, QN-139b is manufactured from a banked, well-characterized induced pluripotent stem-cell (iPSC) clone that has been extensively gene-edited before any patient is selected. This offers huge time and cost-saving advantages over therapies that require modification of an individual patient’s cells.
While a single patient result has a long way to go before being adopted as a clinical treatment, the authors conclude that off-the-shelf iPSC-derived CAR-NK cells may one day give clinicians a rapid, repeatable tool for halting and reversing autoimmune fibrosis far beyond the reach of today’s medications.
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More information:
Xiaobing Wang et al, An iPSC-derived CD19/BCMA CAR-NK therapy in a patient with systemic sclerosis, Cell (2025). DOI: 10.1016/j.cell.2025.05.038
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Universal stem cells reset immunity in a systemic sclerosis patient (2025, July 9)
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