Qihan Bio Announces Breakthrough with iPSC-Derived Dual-Target CAR-NK Therapy QN-139b in First-Ever Successful Treatment of Refractory Systemic Sclerosis

Jun 25, 2025 08:00 CST Updated 08:00

Qihan Biotech

Gene Editing Technology Developer

Editor | Wang Duoyu

Typesetting丨Shuicheng Wen

Systemic Sclerosis（Systemic sclerosis，SSc）It is a chronic autoimmune disease characterized by vascular abnormalities, immune activation, and progressive tissue fibrosis, and its clinical treatment has long faced challenges such as limited drug efficacy, irreversible fibrosis, and high disease heterogeneity. Particularly in diffuse cutaneous systemic sclerosis.（dcSSc）In China, the efficacy of conventional drugs is limited, and the prognosis is poor.

Despite the current autologous hematopoietic stem cell transplantation（HSCT）Or CAR-T cell therapy has made preliminary progress in some refractory cases, but also faces high toxicity reactions.(e.g., CRS, ICANS), preparation individualized restrictions and production standardization issues have seriously hindered its promotion among a wider population of autoimmune disease patients.

June 24, 2025Changzheng Hospital, Naval Medical UniversityXu HujiProfessor Team CollaborationHangzhou Qihan Gene Biotechnology Co., Ltd.，In Cell The journal published an article titled:An iPSC-derived CD19/BCMA CAR-NK therapy in a patient with systemic sclerosisResearch Paper.

The study adoptedUseQihan BiotechDeveloped based onInduced Pluripotent Stem Cells（iPSC）Engineering ofCD19/BCMA Dual-targetCAR-NKCell TherapyQN-139b, and in severe refractoryDiffuse Cutaneous Systemic Sclerosis（dcSSc）The first successful clinical translation was achieved in patients.

The StudyThe World's FirstImportant Breakthrough in the Treatment of Autoimmune Diseases with iPSC-Derived CAR-NK Cells“Off-the-shelf, Low Toxicity, Broad-spectrum Targeting”A new paradigm has been established for the precise treatment of autoimmune diseases, further highlighting Hangzhou Qihan Biotech Co., Ltd.'s globally leading technological advantage in off-the-shelf cell therapy for autoimmune diseases.

QN-139b YesQihan BiotechBased on the high-throughput gene editing technology platform developed over many years and low immunogenicity, while targeting CD19 AndBCMA The two targets to eliminate pathogenicityB Off-the-shelf cell products of cells and plasma cells.

In terms of gene editing technology,QihanThe team edited a total of9 Genes(Knocked in 6 genes — HLA-E, tEGFR, HLA-G, IL-2RF, aCD19-CAR, aBCMA-CAR; knocked out 3 genes — B2M, CIITA, CD16)In order to ensure the safety of the product, the Qihan team selected a non-cutting type of gene editing tool.(Cytosine Base Editor)To avoid genomic rearrangement, targeted transgene insertion into the "safe harbor" of the genome（safe harbor）, and the cells are derived from sequenced monoclonal stem cells to minimize genomic toxicity. In the product design, the research team has addedtEGFR As a safety switch, and innovatively knocked outCD16 Molecules, to reduceNK Cells may pose a risk of exacerbating conditions in patients with autoimmune diseases. Meanwhile, the research team has introduced proprietary intellectual property.NK Survival components and low immunogenicity, enhancedQN-139b The amplification capacity and efficacy in the patient's body.

Cell Preparation Process

Xu HujiLed by ProfessorClinical Team UsesQN-139b Treated oneSevere RefractoryDiffuse Cutaneous Systemic Sclerosis（dcSSc）Patient. The patient is a36 A 20-year-old female who has been suffering from a chronic illness for 20 years, she...16 Raynaud's phenomenon first appeared at the age of ____, accompanied by anti--Scl-70 Strongly Positive Autoantibodies（+++）。18 At the age of , she began to experience thickening of the skin, with erythema and joint pain gradually appearing on her hands and limbs. Over time, skin hardening extended to her face, neck, and chest, leading to severe functional impairment. Although her lungs were normal, three years ago, through a chestCT Interstitial lung disease detected（ILD）Despite receiving various treatments over the years, including methylprednisolone, cyclophosphamide, hydroxychloroquine, methotrexate, mycophenolate mofetil, tocilizumab, and nintedanib ethanesulfonate soft capsules, her condition continued to worsen.

The patient2024 Year8 Month4 First Acceptance in JapanQN-139b Treatment,The dose is6×10⁸Cells, with a total of four doses administered（D0、3、7、10Day). After6 Months of follow-up,QN-139b The overall safety is good, and the patient has no particular complaints of discomfort. In clinical evaluations, the patient reported significant improvement in the overall condition, with objective manifestations including a notable decrease in autoantibodies and the complement returning to normal levels.mRSS The score was significantly reduced.ACR-CRISS Scores improved significantly. Peripheral blood monocyte analysis and proteomic analysis showed that the patient's pathologicalB Cells were cleared, inflammation and fibrosis were suppressed, infiltrating lymphocytes in the affected skin were eliminated, and microvascular reconstruction occurred in the skin.QN-139b Successfully induced the patient to achieve immune reset.

Highlights of the study:

QN-139b is an iPSC-derived CD19/BCMA dual-target CAR-NK cell product;
QN-139b Exhibited Very Low Toxicity in a Patient with Severe Refractory Systemic Sclerosis;
QN-139b reversed fibrosis in this patient and restored their skin and vascular structure;
QN-139b reduced autoantibodies, cleared pathological B cells, and induced immune resetting.

The leader of this clinical trial, Department of Rheumatology and Immunology, Changzheng HospitalXu HujiThe professor stated,Qihan BiotechWith strong and in-depth scientific research capabilities and technical platforms, they are a highly trusted partner.QN-139b As aiPSC SourceTheCAR-NK Cell Products,With generality,iPSC AndNK The Three Major Advantages of Cells. In treatmentRefractory Systemic SclerosisIn the process of,QN-139b Demonstrated good safety characteristics. During the period of6 During the months of follow-up, the patient showed significant clinical improvement, including reductions in autoantibodies and reversal of fibrosis. There remains a substantial unmet need in autoimmune diseases, and we highly anticipate that Hangzhou Qihan Biotech Co., Ltd., relying on its research strength and technology platform, will continue to expand its exploration in autoimmune diseases to help more patients.

Academician of the Chinese Academy of SciencesPei GangSaid,Yang LuhanaThe Qihan team, led by Dr., has深耕多年 in the field of universal off-the-shelf cells, possessing world-leading high-throughput gene-editing technology and accumulating extensive experience in iPSC-derived cells and low immunogenicity. This close collaboration with the clinical team on a breakthrough in autoimmune diseases has opened a new direction for universal off-the-shelf cell therapy and laid a solid foundation for advancing such therapies into large-scale clinical treatment and future widespread application.

Founder and CEO of Hangzhou Qihan Biotech Co., Ltd.Yang LuhanaDr. stated,We are delighted to see this individual with nearly20 Year-long history of autoimmune diseaseThe patient is receivingQN-139b Significant clinical improvement was achieved after treatment, thank you.Xu HujiProfessor Team. In the past few years, Qihan in ChinaiPSC-NK In the exploration of cells, there have been successes and failures, but we have always adhered to our original intention, committed to providing better solutions for patients, and have higher requirements for the safety and efficacy of product design and development. After years of accumulation, Qihan has mastered various strategies to reduce immune rejection of allogeneic cells, and we believe these strategies will be helpful.iPSC-NK Cells、iPSC-T CellsAnd universal typeCAR-T CellsThe development of a variety of generic cellular products, which will be applied to a wide range of patients with autoimmune diseases, providing patients with immune reset and long-term relief solutions.

Related Reading：

July 16, 2024Xu HujiProfessor Team CollaborationShanghai Bangyao Biotechnology Co., Ltd.、Researchers from East China Normal University, inCellThe journal published an article titled:Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosisResearch Paper【2】。

This study utilized CRISPR-Cas9 gene editing technology to genetically engineer CD19-targeted CAR-T cells derived from healthy donors, aiming to address immune rejection issues and thereby developingNew Generation AllogeneicUniversal CAR-T Therapy（TyU19）, and successfullyTreated 1 caseRefractory Immune-Mediated Necrotizing MyopathyPatients, as well as 2 casesDiffuse Cutaneous Systemic SclerosisPatients. During the 6-month follow-up period after treatment, all three patients experienced deep relief of symptoms.The Disease Clinical Response Index score significantly improved, with inflammation and organ fibrosis also being reversed, andNo cytokine release syndrome or other serious adverse events.

It is worth mentioning that this isWorld's First Report of Allogeneic Universal CAR-T Cell Successfully Treating Autoimmune Diseases，Also a top academic journalCellFirst Publication of CAR-T Cell Therapy for Autoimmune DiseasesThis not only represents a critical breakthrough for Bionno Bio in the field of CAR-T, especially allogeneic universal CAR-T for treating autoimmune diseases, but also signifies a qualitative leap in technological differentiation and innovation in the cell and gene therapy sector.

May 29, 2025Xu HujiProfessor Team et al. in Cell Sub-JournalMedPublished an article titled:Allogeneic CD19-targeted CAR-T therapy in refractory systemic lupus erythematosus achieved durable remissionResearch Paper【3】。

The study used allogeneic CD19-targeted CAR-T cell therapy.（TyU19）Successfully TreatedRefractorySystemic Lupus Erythematosus，The therapy was well-tolerated, with the infused CAR-T cells proliferating robustly, effectively eliminating patients' B cells and significantly reducing autoantibodies in the serum. All three patients achieved clinical durable remission as defined by the SRI-4 criteria at the final assessment. These promising results indicate that allogeneic CAR-T cell therapy holds significant potential for treating systemic lupus erythematosus, demonstrating notable safety and clinical efficacy that contribute to disease remission.

Xu HujiThe professor stated,This time inMedThe published results are not only a follow-up to the previous publication inCellA powerful extension of work, and marks a critical leap for the universal CAR-T cell therapy in systemic autoimmune diseases from exploration to translational application.

January 9, 2025Qihan BiotechYang LuhahnIn collaboration with Zhejiang UniversityYellow RiverProfessor TeamIn the Cell Press journalCell Reports MedicinePublished an article titled:CD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells Research Paper【4】。

The study shows that quadruple gene-edited, CD70-targeted iPSC-derived NK cells ——70CAR-iNK, which can effectively target tumor cells and allogeneic T cells, while achieving broad tumor type coverage, superior proliferation ability, and enhancedAntibody-Dependent Cell-Mediated Cytotoxicity（ADCC）And resistance to allogeneic T-cell rejection has great potential in overcoming the current limitations of cell therapy.Is the next generation of universal immune cell therapyA strong candidate.

Paper Link：

1. https://www.cell.com/cell/abstract/S0092-8674(25)00625-7

2. https://www.cell.com/cell/abstract/S0092-8674(24)00701-3

3. https://www.cell.com/med/abstract/S2666-6340(25)00176-X

4. https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(24)00660-8

SettingsStar Marker, so as not to miss exciting tweets

Open Repost

Welcome to share on Moments and WeChat groups.

WeChat Group Addition

To promote the dissemination and exchange of cutting-edge research, we have established severalProfessional Exchange Group, Press and hold the QR code below to add the editor's WeChat and join the group. Due to the large number of applicants, please include a note when adding WeChat:School/Professional/Name, ifPI/Professor, please also indicate.

PointIn View, Convey Your Taste