Single-Cell Multi-Omics Analysis of Equecabtagene Autoleucel in CNS Autoimmune Diseases Published in Science Immunology

On May 10, 2024, Science Immunology, a prominent international academic journal, published a groundbreaking research paper titled "Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity." The paper highlights the comprehensive single-cell multi-omics analysis of the fully human BCMA-targeting autologous CAR-T cell injection (Equecabtagene Autoleucel, Eque-cel, R&D code: CT103A) in treating neuromyelitis optica spectrum disorder (NMOSD). This study is the first to globally describe the dynamic evolutionary pathways of CAR-T cells in autoimmune disease patients, uncovering the molecular attributes of CAR-T cell infiltration in the central nervous system and the mechanism behind immune remodeling during CAR-T therapy for these diseases.

In 2022, IASO Bio published interim results of an investigator-initiated phase I clinical study of Eque-cel in treating NMOSD in Signal Transduction and Targeted Therapy, a sub-journal of Nature. These initial results demonstrated the therapy's safety, tolerability, durable clearance of pathogenic antibodies, and potential clinical efficacy. However, the precise cell kinetics and immunological properties of CAR-T cells in treating central nervous system autoimmune diseases remained largely unexplored.

The study, an investigator-initiated open-label trial (NCT04561557), was led by Professor Wei Wang's team at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. It aimed to evaluate the safety and efficacy of Eque-cel in treating relapsed/refractory antibody-mediated idiopathic inflammatory disorders of the nervous system. Single-cell multi-omics analysis was performed on blood and cerebrospinal fluid (CSF) samples from five relapsed or refractory AQP4-positive NMOSD patients and five multiple myeloma patients treated with Eque-cel. The analysis revealed that only 13% of the B cell immunoglobulin heavy chain variable region (IgVH) sequences overlapped between the peripheral blood and CSF of NMOSD patients, indicating that most B cells in the CSF originated from within the central nervous system rather than the peripheral blood.

The study discovered that chemotactic CAR-T cells could cross the blood-brain barrier and directly eliminate abnormal plasma cells in the central nervous system, promoting the restoration of central immunity. This action reduces autoantibody secretion within sheaths and abnormal immune cell activation, thereby correcting immune disorders in the central nervous system and resetting the immune system of NMOSD patients. The research showed that CAR-T cells in immune disease patients predominantly exhibit a CD8+ cycling CAR-T cell phenotype with reduced cytotoxic function compared to the control group. These characteristics explain the relatively low grade of cytokine release syndrome (CRS) and shorter survival time of CAR-T cells after therapy, which facilitates earlier immune remodeling and underscores the safety of Eque-cel in autoimmune diseases.

Professor Wei Wang emphasized the significance of the findings, stating that the study represents the first extensive single-cell multi-omics analysis of various body fluids from NMOSD patients, mapping the dynamic evolutionary pathways of CAR-T cells at the cellular and molecular levels. He highlighted the ability of chemotactic CAR-T cells to cross the blood-brain barrier and target abnormal immune cells in the central nervous system, crucial for treating immune abnormalities in this region. Differences in CAR-T cell characteristics between autoimmune and tumor patients were noted, offering insights for refining CAR-T cell therapies for autoimmune diseases.

Ms. Jinhua Zhang, Founder and CEO of IASO Bio, expressed satisfaction with the publication of another Eque-cel research achievement in Science Immunology. This is the third significant academic article resulting from the collaboration between IASO Bio and Professor Wang’s team at Tongji Hospital this year, further validating the efficacy, safety, and longevity of CAR-T therapy in treating autoimmune diseases. IASO Bio is committed to advancing CAR-T products for autoimmune conditions, having obtained Investigational New Drug (IND) approvals for multiple autoimmune diseases in China and the United States. The company plans to expedite these projects and expand global collaborations to provide safer and more effective treatments for autoimmune patients worldwide.