Bioray Bio Achieves Global Breakthrough with Allogeneic Universal CAR-T Therapy for Lupus: First to Demonstrate Deep Remission and Enhanced Safety
BRL Medicine
Cell and Gene Therapy Drug Developer
On May 13, 2025, BRL Medicine Inc., a Shanghai-based biotechnology company focusing on gene and cell therapy (hereinafter referred to as "BRL Medicine"), announced that it hasDepartment of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityProfessor Tong Hongyan, Rheumatology and Immunology DepartmentProfessor Lin Jin, andSchool of Life Sciences, East China Normal UniversityProfessor Liu Mingyao、Professor Du BingLeading Scientific Research TeamCooperation, officially on May 8th, in the international academic journalCell ResearchPublished titled:“Allogeneic anti-CD19 CAR-T cells induce remission in refractory systemic lupus erythematosus”Clinical research paper. This isFirst Global Report on the Use ofSuccessful Case of Allogeneic Anti-CD19 CAR-T Cells (TyU19) with CRISPR/Cas9 Gene Editing in the Treatment of Relapsed/Refractory Systemic Lupus Erythematosus (SLE). The study results demonstrate that TyU19 cells can achieve rapid and deep clinical remission in SLE treatment while exhibiting excellent clinical safety. This breakthrough outcome establishes a new paradigm for the treatment of autoimmune diseases.
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May 8, 2025Cell ResearchIssued by
Notably, the TyU19 used in this study is a proprietary universal cell platform (TyUCell) developed by the research team led by Professor Mingyao Liu, founder & chairman of BRL Medicine, and Professor Bing Du.®) , since 2016, after 8 years of scientific research and multiple technical iterations, the world's first allogeneic universal CAR-T cell therapy product targeting the CD19 antigen has been developed. This product is characterized by high accessibility, low cost, and stable quality, among other features. It can be said that the breakthrough clinical results obtained from this product also mark BRL Medicine as once again taking a leading position in the field of universal CAR-T technology, establishing BRL Medicine's leadership in the industry.
TyU19 Technical Breakthrough Solves the Core Challenge of Allogeneic CAR-T Therapy
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease characterized by abnormal B-cell activation and the production of autoantibodies, with limited efficacy of traditional immunosuppressants in some patients. Although autologous CAR-T therapy has shown initial success in SLE, it faces challenges such as long individualized preparation time and high costs, making allogeneic CAR-T cells a promising alternative due to their homogeneity and immediate availability. However, obstacles including graft-versus-host disease (GVHD), host rejection responses, gene-editing-related genotoxicity risks, and infection risks from excessive immunosuppression have restricted its broader clinical application.
In this investigator-initiated clinical study (IIT),The research team evaluated the safety and efficacy of allogeneic CD19-targeted CAR-T cells (TyU19) in refractory systemic lupus erythematosus.TyU19, developed by BRL Medicine, primarily utilizes healthy donor cells and employs a sophisticated multi-gene, selective gene-editing strategy to perform multiple precise edits on donor T cells (knocking out the TRAC, HLA-A, HLA-B, CIITA, and PD-1 genes) to fundamentally eliminate the risk of host rejection and graft-versus-host disease (GVHD).
Between September 2023 and September 2024, the study enrolled four female patients aged 22-24 with relapsed/refractory SLE. Their baseline SELENA-SLEDAI scores ranged from 14 to 26, all with a history of multi-system involvement (some had a previous history of lupus encephalitis) and were unresponsive to conventional immunosuppressants and biologics treatment.All patients receivedAfter TyU19 cell infusion treatment, the clinical results showed:
Significant efficacy:All patients achieved sustained SRI-4 response criteria within 3 months, showing continuous improvement in clinical signs and symptoms. Between 3 to 6 months, the SELENA-SLEDAI disease activity score dropped to 0, with complete remission of clinical symptoms such as arthritis, alopecia, and vasculitis; complement levels and key antibody indicators returned to normal.
Immune Remodeling:All patients achieved deep B-cell depletion within one week post-infusion, with abnormal B-cell activation being profoundly suppressed. The proportion of memory B cells and plasma cells—the main culprits behind autoantibody production—decreased significantly, suggesting that TyU19 may inhibit autoantibody production by reshaping B-cell homeostasis.
Excellent Safety:All patients only experienced grade 1 cytokine release syndrome (CRS, transient fever), and during the treatment period, no patients developed immune effector cell-associated neurotoxicity syndrome (ICANS) or graft-versus-host disease (GVHD). Grade 3-4 adverse events were mainly neutropenia and lymphopenia, with no severe infections occurring.
Clinical Response and Immune Reconstitution of TyU19 in the Treatment of SLE
FromMilestone of Laboratory to Clinical Translation,TyU19Huge Potential
For the breakthrough progress achieved in this study,Corresponding Author, Department of Hematology, The First Affiliated Hospital of Zhejiang University School of MedicineTong HongyanThe professor stated:"CAR-T cell therapy has made revolutionary progress in hematologic malignancies, transforming the treatment landscape of blood cancers. Excitingly, the successful treatment of patients with relapsed/refractory SLE in this case, particularly one patient who discontinued all hormones and immunosuppressive drugs after TyU19 cell therapy and achieved drug-free remission, is remarkable. This not only suggests that allogeneic CAR-T could become a highly promising treatment for SLE patients unresponsive to conventional therapies (such as hormones and biologics), but this research also lays an important clinical foundation for allogeneic CAR-T in treating autoimmune diseases, potentially establishing a new paradigm for autoimmune disease treatment."
Regarding this cooperation,Corresponding Author of the Paper, Founder of BRL MedicineLiu MingyaoThe professor said"Traditional allogeneic CAR-T therapy has always posed significant infection risks to patients due to excessive immune suppression, along with challenges such as short persistence in the body and suboptimal efficacy, greatly limiting its clinical accessibility. TyU19, used in this clinical study, was developed by BRL Medicine Inc. over eight years of dedicated research using gene-editing technology, effectively addressing these issues. Under a less intensive lymphodepletion regimen compared to autologous CAR-T, TyU19 achieved long-term persistence and effective cytotoxicity in patients. Its safety, efficacy, and other key metrics matched or even surpassed those of traditional autologous CAR-T. This is the primary reason TyU19 has become the world’s first successful allogeneic off-the-shelf CAR-T therapy for treating autoimmune diseases."Previously, BRL Medicine collaborated with Professor Xu Hujin from Shanghai Changzheng Hospital to successfully treat three patients with refractory autoimmune diseases (one case of refractory immune-mediated necrotizing myopathy and two cases of diffuse cutaneous systemic sclerosis) using TyU19. This study is also the world's first published inCellThe successful case of treating autoimmune diseases has been highly praised both in China and internationally, and has been selected as one of the top ten scientific advances in China in 2024."
In addition,Corresponding author of the paper, BRL MedicineDu BingThe professor also said:"After years of technical research and iterative upgrades, TyU19 has shown excellent performance in the earlier treatment of B-cell acute lymphoblastic leukemia (B-ALL), multiple refractory autoimmune diseases, and now in the treatment of SLE. This fully demonstrates that our new generation of allogeneic CAR-T products has successfully achieved technical upgrade validation and has effectively established the pharmaceutical and clinical development pathways. Moreover, this clinical data strongly confirms that our allogeneic CAR-T can not only rapidly eliminate pathogenic cells but also achieve long-term remission through immune system remodeling, even allowing some patients to摆脱药物依赖. In the future, we will continue to optimize the process and promote the普及of this therapy in various autoimmune diseases, enabling more patients to access and afford innovative treatments."
About“TyU19”
TyU19 is based on BRL Medicine's proprietary universal cell platform (TyUCell).®) A brand-new generation of allogeneic universal CAR-T product targeting CD19 developed byIt mainly achieves immune escape and functional optimization of allogeneic T cells through multiple gene-editing technologies, fundamentally avoiding the risks of graft-versus-host disease (GVHD) and host versus graft (HVG) rejection. This perfectly overcomes the most critical technical barrier in the development of allogeneic universal CAR-T products: the rejection of allogeneic cells by the patient's immune system. On the basis of ensuring the safety and efficacy of cellular products, it truly realizes the universalization of immune cell therapy products. Currently, BRL Medicine has relied on this technological product respectively.Focusing on the treatment of hematological tumors and autoimmune diseases, BRL Medicine has developed the product pipelines BRL-301 and BRL-303.Among them, BRL-301 has been approved for IND in China for two indications in the field of hematological tumors: relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) and relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL), and is accelerating the advancement of registrational clinical trials.
It can be said that the existing clinical research has fully validated the application potential of BRL Medicine's TyU19 allogeneic CAR-T in the treatment of multiple indications, including tumors and autoimmune diseases.Compared with similar products at home and abroad,BRL Medicine's UCAR-T Therapy Has Three Core Advantages:
As an "off-the-shelf" universal CAR-T product, TyU19 eliminates the need for autologous cell collection and customized production. A single batch can meet the treatment needs of over 200 patients, significantly reducing production costs while markedly shortening patient waiting times. Its HLA-matching-free feature makes it especially suitable for R/R B-NHL patients with rapidly progressing conditions or impaired autologous cell function, offering a "timely rain"-like treatment option for those who have failed traditional therapies.
TyU19 does not require additional lymphodepletion or immunosuppression for patients. By adopting a conventional or even lower lymphodepletion regimen, it can achieve complete elimination of tumor cells while effectively avoiding risks associated with excessive immunosuppression, such as infection, neutropenia, and slow lymphocyte recovery. Existing clinical trial data show that no patients treated have experienced Grade ≥3 cytokine release syndrome (CRS) or neurotoxicity (ICANS), and the incidence of infection is lower than that of similar products, demonstrating its excellent clinical safety.
BRL Medicine Enhances TyU19's Proliferation and Long-Term Persistence In Vivo by Selecting Healthy Donor T Cells and Optimizing Expansion Processes. In the early-stage clinical trials, TyU19 has demonstrated significant and durable tumor clearance capabilities, with all tested tumor patients achieving complete remission (CR or CRi). It exhibited robust proliferation and long-term persistence in patients, offering the potential for prolonged survival.
In the future, BRL Medicine will rapidly advance multi-center clinical trials in China for the new generation of allogeneic universal CAR-T (UCAR-T) and actively explore the application of UCAR-T technology in hematologic tumors, solid tumors, and autoimmune diseases, benefiting a wide range of patients.