Innovative Off-the-Shelf Stem Cell Therapy Restores Immunity in Systemic Sclerosis Patient

Research conducted by Naval Medical University's Changzheng Hospital in China has demonstrated that an off-the-shelf cell therapy derived from induced pluripotent stem cells (iPSCs) effectively reduced severe skin and organ scarring in a woman with systemic sclerosis, a debilitating autoimmune disease. Systemic sclerosis, or scleroderma, progressively damages tissues through immune dysfunction, vessel collapse, and excessive collagen production, often resisting conventional treatments such as immunosuppressants, biologics, and anti-fibrotic drugs, leading to a high 10-year mortality rate of approximately 40%.

The study, published in the journal Cell, details how researchers engineered a universal cell therapy called QN-139b aimed at eliminating pathogenic B cells responsible for tissue fibrosis. These allogeneic cells were created using gene-editing techniques on human iPSCs, knocking out certain genes like B2M, CIITA, and CD16, while inserting others such as HLA-E, HLA-G, interleukin-2 receptor fusion, and chimeric antigen receptors targeting CD19 and BCMA. The process allowed the cells to be prepared in advance, providing a ready-to-use treatment option.

The therapy was administered to a 36-year-old woman with extensive diffuse cutaneous systemic sclerosis at Changzheng Hospital in Shanghai. Prior to infusion, the patient's immune system was suppressed with cyclophosphamide and fludarabine, followed by four intravenous infusions of 6×10^8 QN-139b cells on days 0, 3, 7, and 10. This resulted in a rapid decline in B cell counts, with near-total depletion by day 7. Over the following six months, antibody levels decreased steadily. Correspondingly, improvements in skin fibrosis, assessed by the modified Rodnan Skin Score and ultrasound elastography, were recorded. Nailfold capillaroscopy showed restoration of capillary loops and fewer hemorrhagic infarcts, while high-resolution lung scans revealed reduced ground-glass opacities and reticular patterns. Cardiac imaging indicated decreased late gadolinium enhancement, signifying diminished tissue inflammation.

Importantly, the patient experienced no severe adverse effects such as cytokine-release syndrome, neurotoxicity, or graft-versus-host disease. The use of banked, extensively gene-edited iPSC lines offers significant advantages, including reduced time and costs compared to personalized therapies. Although this is a preliminary result from a single patient, the findings suggest that off-the-shelf iPSC-derived natural killer cell therapies could become a rapid and effective tool for reversing autoimmune fibrosis, potentially transforming the treatment landscape for systemic sclerosis and related autoimmune conditions.

This groundbreaking study highlights the potential of stem cell engineering to develop safer, more accessible treatments and paves the way for future clinical trials exploring universal cell therapies for complex autoimmune diseases.