Hangzhou Qihan Biotech Co., Ltd. has achieved a significant milestone in autoimmune disease treatment with the first-ever clinical application of iPSC-CAR-NK cells, demonstrating remarkable efficacy in treating refractory systemic sclerosis (SSc). The groundbreaking results, published in Cell, showcase the therapeutic potential of the company's off-the-shelf, dual-targeting cell product QN-139b in successfully inducing immune reset in a patient with nearly two decades of disease history.
Revolutionary Cell Therapy Design
QN-139b represents a universal, dual-targeting CAR-NK product engineered to eliminate pathogenic B cells and plasma cells by targeting both CD19 and BCMA. The therapy was developed using Qihan's high-throughput gene editing platform and incorporates sophisticated safety and efficacy features, including edits to nine genes and non-cleaving editing tools to prevent chromosomal rearrangements.
The product's advanced design includes transgene insertion into genomic "safe harbor" sites and production from sequenced monoclonal iPSC lines to minimize genomic toxicity. To enhance safety specifically for autoimmune patients, QN-139b features a tEGFR safety switch and an innovative CD16 knockout designed to reduce the risk of disease flares. The therapy also incorporates proprietary persistence-enhancing elements and a low-immunogenicity design to strengthen in vivo expansion and therapeutic durability.
Clinical Success in Refractory Case
The reported study involved a 36-year-old female patient with diffuse cutaneous systemic sclerosis (dcSSc) spanning nearly 20 years. Beginning August 4, 2024, the patient received four doses of QN-139b at 6 × 10⁸ cells per dose on days 0, 3, 7, and 10. After six months of follow-up, the treatment demonstrated both a strong safety profile and remarkable clinical efficacy.
The therapeutic outcomes included significant reduction in autoantibodies and normalization of complement levels, dramatic improvement in modified Rodnan skin score (mRSS), and enhanced ACR-CRISS score. Histological analysis revealed compelling evidence of B cell clearance, fibrosis suppression, lymphocyte depletion in affected tissues, and skin microvascular remodeling.
Industry Impact and Future Implications
"We are proud to see a patient with nearly two decades of systemic sclerosis achieve such meaningful clinical improvement following QN-139b treatment," commented Dr. Luhan Yang, Founder and CEO of Hangzhou Qihan Biotech Co., Ltd. "Our years of innovation in reducing allogeneic immune rejection now empower not only iPSC-NK but also iPSC-T and universal CAR-T platforms—offering renewed hope for patients with autoimmune diseases worldwide."
The study was conducted in collaboration with Professor Huji Xu's clinical team at Shanghai Changzheng Hospital, representing Qihan's global leading technology for the cell therapy field. This breakthrough marks the first application of iPSC-CAR-NK cells in autoimmune disease treatment, potentially opening new therapeutic avenues for patients with severe autoimmune conditions who have limited treatment options.
The successful immune reset achieved in this refractory SSc patient suggests that genetically edited allogeneic iPSC-CAR-NK products could serve as effective immune-modulatory therapies for severe autoimmune diseases, offering hope for patients worldwide who face limited therapeutic options with current treatments.
