The academic results of single-cell multiomic analysis of Iggene cel injection for the treatment of central nervous system immune diseases were published in Science Immunology

NANJING, CHINA AND SAN JOSE, Calif., May 11, 2024 /PRNewswire/ --

May 10, 2024, an international authoritative academic journal Science子刊 《Science Immunology》（ 《Science -免疫》）正式发表了驯鹿生物全人源靶向BCMA嵌合抗原受体自体T细胞注射液（伊基奥仑赛注射液，研发代号CT103A）治疗视神经脊髓炎谱系疾病（NMOSD）患者的单细胞多组学分析的研究论文——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 patients with autoimmune diseases, analyze the molecular characteristics of CAR-T cell central infiltration, reveal the mechanism of central nervous system immune remodeling in the treatment of central nervous system immune diseases by CAR-T, and elucidate the molecular differences of CAR-T cells between patients with autoimmune diseases and cancer patients at the cellular and molecular levels.

In 2022, IASO Biotech published the interim results of the investigator-initiated phase I clinical study of Igta-cel injection for the treatment of neuromyelitis optica spectrum disease (NMOSD) in Signal Transduction and Targeted Therapy (IF=38.1), which preliminarily demonstrated the good tolerability and safety of Igneucta-cel injection in NMOSD, the long-lasting pathogenic antibody clearance effect, and the potential clinical efficacy. However, the cytodynamic and immunological characteristics of CAR-T therapy for central nervous system immune diseases are still unclear.

The study is an investigator-initiated exploratory clinical study (NCT04561557) to evaluate the safety and efficacy of infusion of Igneucta-cel injection in the treatment of relapsed and refractory antibody-mediated idiopathic inflammatory diseases of the nervous system.

In this study, single-cell multiomic analysis was performed on the blood and cerebrospinal fluid samples of 5 patients with relapsed and refractory AQP4-positive NMOSD and 5 patients with multiple myeloma who received Igaeottael injection to study the characteristics of CAR-T cells in patients with autoimmune diseases in vivo. The study found that there was only 13% overlap in the variable region (IgVH) sequence of B-cell immunoglobulin in the peripheral blood and cerebrospinal fluid of NMOSD patients, indicating that the B cells in the cerebrospinal fluid were mostly derived from the intrinsic B cells of the central nervous system rather than from the peripheral blood.

and those with chemotaxis CAR-T cells can penetrate the blood-brain barrier and enter the center, directly kill the abnormal plasma cells of the central nervous system, reduce the secretion of autoantibodies in the sheath and the abnormal activation of immune cells, thereby correcting the central nervous system immune disorder in patients with NMOSD and facilitating the central immune reconstitution of patients.

Studies have shown that the cytotoxic CAR-T cell phenotype of CD8+ is dominant in patients with immune diseases, and the killing function of CAR-T cells is reduced compared with the control group. The above characteristics explain the relatively mild severity of CRS and the relatively short duration of CAR-T cells in patients with immune diseases, which is conducive to the early immune reconstitution of patients.

The favorable safety profile of Iggene autoleucel injection in autoimmune diseases was further confirmed

。

The principal investigator of this study,

Professor Wang Wei of Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology said

"With the emergence of innovative clinical studies of CAR-T therapy for autoimmune diseases in different countries and regions around the world, experts around the world are now paying more and more attention to and recognizing the application prospects of this innovative cell therapy for patients with relapsed and refractory immune diseases. This study is the world's first in-depth analysis of multiple body fluids of NMOSD patients by single-cell multi-omics, and depicts the dynamic evolution of CAR-T cells into the body of immunological patients at the cellular and molecular level. In particular, we found that CAR-T cells with chemotaxis properties can more easily penetrate the blood-brain barrier and enter the central nervous system to directly kill abnormal immune cells in the central nervous system, which is very important for the treatment of immune abnormalities in the central nervous system. At the same time, by comparing with CAR-T cells in cancer patients, we found that there are many different characteristics of CAR-T cells in autoimmune patients and CAR-T cells in cancer patients, which is expected to provide an important scientific basis for the iterative improvement of CAR-T cell therapy products for immune diseases in the future. "

Ms. Jinhua Zhang, founder and CEO of IASO Biotech, said

"We are very pleased to see the publication of another research result of Igta-autoleucel injection for the treatment of autoimmune diseases in Science Immunology, which is the third academic article in the field of autoimmunity published in an international authoritative journal in collaboration with the team of Professor Wang Wei of Wuhan Tongji Hospital this year. The results of this study once again create a "world first", further verifying the efficacy, safety and durability of CAR-T therapy for the treatment of autoimmune diseases, which once again strengthens IASO Biotech's determination to continue to focus on the development of CAR-T products in the field of autoimmunity. At present, IASO Bio has received clinical approval for autoimmune diseases including neuromyelitis optica and myasthenia gravis in China and the United States, and plans to accelerate the progress of these programs. In terms of BD collaboration, in 2022, we entered into a global exclusive license agreement with Cabaletta Bio, a U.S.-based cell therapy company, under which we granted Cabaletta the exclusive rights to develop, manufacture and commercialize the clinically validated fully human CD19 sequence in the field of CAR-T autoimmunity. We will actively expand more global BD cooperation in the field of autoimmunity, accelerate product development, and enable autoimmune patients around the world to use safer and more effective drugs faster. "