Science and Technology

Breakthrough CAR-T Cell Therapy Offers Hope for Autoimmune Disease Patients

SHANGHAI, NANJING, China, and SAN JOSE, Calif., May 10, 2024 – In a remarkable advancement within the field of medical research, the renowned international academic journal, Science Immunology, recently published an illuminating research paper titled "Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity". This groundbreaking study provides an in-depth examination of the advanced single-cell multi-omics analysis applied to a cutting-edge therapy known as Equecabtagene Autoleucel (or Eque-cel). Renowned for its ability to target BCMA with fully human autologous CAR-T cells, Eque-cel is emerging as a potential treatment for patients suffering from neuromyelitis optica spectrum disorder (NMOSD), a devastating autoimmune condition.

Pioneering Research in Autoimmune Disease Treatment

The researchers, for the first time ever, have traced the dynamic evolutionary pathways of CAR-T cells in the fight against autoimmune diseases. They have uncovered the unique molecular traits that enable CAR-T cells to penetrate central nervous system tissues, thereby shedding light on the intricate mechanism of immune reconstruction during therapy. This exceptional work goes several steps further by identifying the molecular disparities when comparing CAR-T cell functionality in autoimmune diseases to that observed in cancer treatments.

In 2022, IASO Bio unveiled interim outcomes from a phase I clinical study instigated by investigators. Published in Signal Transduction and Targeted Therapy, a sub-journal of Nature, these preliminary findings indicated favorable tolerability and safety profiles. Additionally, the lasting removal of pathogenic antibodies and suggested clinical benefits were documented for Eque-cel in NMOSD patients, yet the detailed cell kinetics and immunological characteristics remained largely unexplored.

Unraveling the Mysteries of CAR-T Cell Therapy

This open-label study - investigator-initiated and spearheaded by Professor Wei Wang's team at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology – aimed to rigorously assess the safety and effectiveness of Eque-cel. This was done for patients affected by relapsed, refractory, antibody-mediated idiopathic inflammatory disorders affecting the nervous system (NCT04561557). The team's approach employed single-cell multi-omics analysis on both the blood and cerebrospinal fluid samples from participants, revealing several key findings.

Analyzing the blood and cerebrospinal fluid (CSF) samples from five NMOSD patients with recurring symptoms and five multiple myeloma patients treated with Eque-cel, the study probed into the in vivo attributes of CAR-T cells in patients with autoimmune maladies. Remarkably, only a 13% match was found in the B cell immunoglobulin heavy chain variable region (IgVH) sequences when comparing peripheral blood to CSF in NMOSD individuals. This suggests that the central nervous system predominantly houses its own distinct B cells, as opposed to them being sourced from peripheral circulation.

The study illuminated that CAR-T cells, which possess chemotactic abilities, have the capacity to traverse the blood-brain barrier and directly target and eliminate aberrant plasma cells in the central nervous system. This strategic action not only curtails the production of autoantibodies within the CNS, but also mitigates the abnormal activation of immune cells. Consequently, NMOSD patients may experience a reorientation and resetting of their immune system.

Deciphering the Immune Reset: Findings from the Study

Moreover, the research highlighted that within individuals with immune disorders, CAR-T cells generally display a CD8+ cycling CAR-T cell phenotype. A notable decrease in cytotoxic capabilities in comparison to a control group was observed, which explains the observed lower grades of Cytokine Release Syndrome (CRS) and the relatively shorter lifespans of CAR-T cells post-therapy in immune disease patients. This finding supports the potential for earlier immune restructuring in these individuals and bolsters the evidence pointing to Eque-cel's safety within the realm of autoimmune diseases.

Insights from the Pioneering Team

Professor Wei Wang, the principal investigator of the study, shared his insights. He emphasizes the mounting global interest and recognition of innovative cell therapy application in treating relapsed and refractory immune diseases. The study pioneered a comprehensive single-cell multi-omics analysis across various bodily fluids in NMOSD patients, thereby mapping the intricate cellular and molecular dynamics of CAR-T cells within individuals battling immune diseases. The revelation that chemotactic CAR-T cells can penetrate the central nervous system to directly annihilate abnormal immune cells signifies a major therapeutic breakthrough for central nervous system immune aberrations. This research also delivers crucial scientific insights that will refine and advance CAR-T cell therapies tailored for autoimmune conditions.

Ms. Jinhua Zhang, Founder and Chief Executive Officer of IASO Bio, also expressed her enthusiasm regarding the impactful publication of the research in Science Immunology. This publication marks the third significant scholarly article on autoimmunity resulting from the collaborative efforts of IASO Bio with Professor Wang's team at Tongji Hospital in Wuhan within the year. These cumulative research milestones solidify the effectiveness, safety, and durability of CAR-T therapy in treating autoimmune diseases, reinforcing IASO Bio's commitment to concentrate on the development of CAR-T therapies catered to autoimmunity.

IASO Bio's Ascent in Autoimmune Research

This year alone, IASO Bio has achieved IND approvals for various autoimmune indications across the United States and China, including NMOSD and myasthenia gravis (MG). There is a concerted effort to hasten the progress of these projects. IASO Bio's strategic business development collaborations in the field of autoimmunity were further strengthened in 2022 when they entered into a licensing agreement with Cabaletta Bio, a cell therapy company based in the US. IASO granted Cabaletta Bio exclusive rights to develop, manufacture, and commercialize CAR-T therapies using IASO's clinically proven, fully human CD19 binder to combat autoimmune diseases on a global scale.

Currently, the developmental stages are moving forward, with IND approvals granted for several autoimmune disorders, among them systemic lupus erythematosus (SLE) / lupus nephritis (LN), idiopathic inflammatory myopathies (IIM), systemic sclerosis (SSc), and generalized myasthenia gravis (gMG). With clinical trials advancing steadily, IASO Bio remains actively engaged in seeking to broaden its international business development collaborations within the autoimmune sphere to expedite product development, thereby ensuring sooner access to safer and more efficacious treatments for autoimmune patients globally.

A Closer Look at IASO Bio

IASO Bio stands out as a pioneering biopharmaceutical company, intensively involved in pioneering the discovery and development of novel cell therapies and biologics for battling oncological and autoimmune diseases. The company boasts expansive capabilities that extend across the entire spectrum of drug development—from initial discovery phases, through clinical development and regulatory approval processes, to commercial production stages.

With an impressively diversified portfolio featuring over ten novel products, including the innovative Equecabtagene Autoleucel, IASO Bio has made significant strides in the pharmaceutical landscape. Equecabtagene Autoleucel has the distinction of having received both New Drug Application (NDA) approval from China's National Medical Products Administration (NMPA) and U.S. FDA IND approval for treatment of RRMM, showcasing global recognition and trust.

Powered by a dynamic management team, a rich vein of innovative product pipelines, exceptional GMP production facilities, and integrated manufacturing and clinical competencies, IASO Bio is determined to deliver transformative, curative therapies that meet the dire medical needs of patients both in China and globally. Interested parties and stakeholders can learn more about the company and its endeavors by visiting their website at http://www.iasobio.com or through their LinkedIn profile at www.linkedin.com/company/iasobiotherapeutics.

In conclusion, IASO Bio stands poised at the forefront of a medical revolution, championing innovative treatments that promise to transform the lives of patients around the world. Through its application of state-of-the-art technologies and steadfast dedication to scientific excellence, the world eagerly awaits the next chapters of discovery and development that IASO Bio will write in the annals of medicine.

SOURCE: IASO Bio