Iaso Bio Announces Publication of Single-Cell Multi-Omics Study on BCMA CAR-T Therapy for Central Nervous System Autoimmune Diseases in Science Immunology
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On May 10, 2024, the international authoritative academic journal Science Immunology, a sub-journal of Science, officially published a research paper on the single-cell multi-omics analysis of IASO Bio's fully human BCMA-targeted chimeric antigen receptor autologous T-cell injection (Equecabtagene Autoleucel Injection, R&D code CT103A) for the treatment of patients with neuromyelitis optica spectrum disorder (NMOSD) — Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity. This paper is the first in the world to depict the dynamic trajectory of CAR-T in autoimmune disease patients, analyze the molecular characteristics of CAR-T cell infiltration in the central nervous system, reveal the mechanism of central nervous system immune remodeling in CAR-T treatment of autoimmune diseases, and elucidate the molecular differences between CAR-T cells in autoimmune disease patients and cancer patients at the cellular and molecular levels.
IASO Bio was published in the Nature sub-journal Signal Tra in 2022Induction and Targeted Therapy (IF=38.1) published the interim results of a Phase I investigator-initiated clinical study on the use of Equecabtagene Autoleucel Injection for treating Neuromyelitis Optica Spectrum Disorder (NMOSD). The study preliminarily demonstrated good tolerability and safety of Equecabtagene Autoleucel Injection in NMOSD, persistent clearance of pathogenic antibodies, and potential clinical efficacy. However, the cell kinetics and immunological characteristics of CAR-T therapy for central nervous system autoimmune diseases remain unclear.
This study is an investigator-initiated, open-label exploratory clinical trial (NCT04561557) evaluating the safety and efficacy of infusion of Icarus Bio's Iciclenin injection in treating relapsed or refractory antibody-mediated idiopathic inflammatory neurological diseases. The study is led by Professor Wang Wei's team from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
This study involved 5 patients with AQP4-positive NMOSD who were treated with Ixcell injection and 5 other patients in the same period.Multiple MyelomaSingle-cell multi-omics analysis of blood and cerebrospinal fluid samples from patients to study the characteristics of CAR-T cells in autoimmune disease patients. The study found B cells in the peripheral blood and cerebrospinal fluid of NMOSD patients.Immunoglobulin Heavy ChainThe variable region (IgVH) sequences show only a 13% overlap, indicating that B cells in the cerebrospinal fluid are mostly derived from B cells intrinsic to the central nervous system rather than from peripheral blood.CAR-T cells with chemotactic properties can penetrateBlood-Brain BarrierEntering the central nervous system, directly killing abnormal plasma cells in the CNS, reducing intrathecal autoantibody secretion and abnormal immune cell activation, thereby correcting the immunological disorder state in NMOSD patients' central nervous system, which is beneficial for the central immune reconstruction of patients.。Studies have shown that in patients with autoimmune diseases, CAR-T cells are predominantly composed of the CD8+ cytotoxic CAR-T cell phenotype, and their cytotoxic function is reduced compared to the control group. These characteristics explain the outcomes in autoimmune disease patients after CAR-T therapy.CRSThe relatively mild severity and the relatively short persistence of CAR-T cells are beneficial for patients to achieve immune reconstitution as early as possible.Further confirmed the good safety of IASO Bio's injectable drug in autoimmune diseases.。
The principal investigator of this clinical study, Professor Wang Wei from Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologySaid, "As innovative clinical research on CAR-T therapy for autoimmune diseases continues to emerge in different countries and regions around the world, global experts are increasingly valuing and recognizing the promising application of this novel cell therapy for patients with relapsed and refractory immune disorders. Our study is the world's first to conduct an in-depth single-cell multi-omics analysis of various body fluids from NMOSD patients, depicting the dynamic evolution of CAR-T cells within immune disease patients at the cellular and molecular levels. Particularly, we discovered that CAR-T cells with chemotactic properties are more likely to penetrate the blood-brain barrier and enter the central nervous system, directly eliminating abnormal immune cells there. This finding is crucial for treating immune abnormalities in the central nervous system. Additionally, by comparing CAR-T cells in autoimmune patients with those in cancer patients, we identified many distinct characteristics of CAR-T cells in autoimmune patients, which could provide important scientific evidence for subsequent product iteration and improvement of CAR-T cell therapies for immune diseases."
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Ms. Jin Hua Zhang, Founder and Chief Executive Officer of IASO Bio"It is a great pleasure to see another research achievement on the use of Idecabtagene Vicleucel Injection for treating autoimmune diseases published in Science Immunology. This marks the third academic article in the autoimmune field that IASO Bio has collaborated on with Professor Wang Wei's team from Wuhan Tongji Hospital, published in an internationally authoritative journal this year. Once again, this research achievement represents a 'world-first,' further validating the efficacy, safety, and durability of CAR-T therapy for treating autoimmune diseases. It also reaffirms IASO Bio’s commitment to focusing on the development of CAR-T products for autoimmune indications. Currently, IASO Bio has received clinical approvals in China and the United States for autoimmune diseases such as neuromyelitis optica and myasthenia gravis, and plans to accelerate the progress of these projects. In terms of BD collaboration, in 2022, we reached a global exclusive licensing agreement with Cabaletta Bio, a U.S.-based cell therapy company. We granted Cabaletta the globally exclusive rights to develop, manufacture, and commercialize CAR-T products using our clinically validated fully human CD19 sequence for autoimmune applications. The product has already received IND approval for multiple autoimmune indications, including systemic lupus erythematosus/lupus nephritis, idiopathic inflammatory myopathy, systemic sclerosis, and myasthenia gravis, and its clinical trials are proceeding steadily. We will actively expand more global BD collaborations in the autoimmune field to accelerate product development, enabling patients with autoimmune diseases worldwide to access safer and more effective treatments sooner."
Source: IASO Bio