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688 The Therapeutic Efficacy of CD19 Chimeric Antigen Receptor T Cells in Immune Thrombocytopenia Model

Program: Oral and Poster Abstracts
Type: Oral
Session: 311. Disorders of Platelet Number or Function: Clinical and Epidemiological: Innovative Treatments for Immune Thrombocytopenia
Hematology Disease Topics & Pathways:
Fundamental Science, Research, Bleeding and Clotting, autoimmune disorders, Biological therapies, platelet disorders, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Immune Disorders, Therapies
Monday, December 11, 2023: 11:00 AM

Yun Wang1*, Fengjiao Han1*, Qiuyu Guo, MBBS2*, Qi Feng3*, Jun Peng3*, Ming Hou3* and Miao Xu, MD, PhD4*

1Department of Hematology, Cheeloo College of Medicine, Qilu Hospital of Shandong University, Jinan, China
2Department of Hematology, Qilu Hospital of Shandong University, Jinan, China
3Qilu Hospital of Shandong University, Jinan, China
4Department of Hematology, Qilu Hospital of Shandong University, Jinan, AL, China



ITP is a hemorrhagic autoimmune disease characterized by excessive platelet destruction and impaired platelet production, resulting in a high risk of bleeding. The pathogenesis of ITP involves immune intolerance towards platelet antigen, with platelet autoantibodies produced by plasma cells playing a significant role. Current treatments targeting this pathogenesis mainly rely on CD20 monoclonal antibodies, such as rituximab. However, as CD20 expression is present at the pre-B cell and mature B cell stages but absent on the surface of mature plasma cells. This can explain why a subset of autoantibody-positive patients do not respond to B-cell depletion therapy. CAR-T cell therapy, a form of adoptive cellular immunotherapy, has shown great potential in hematological malignancies and solid tumors. Recent studies have demonstrated its potential effectiveness of CAR-T cell therapy in various autoimmune diseases. CD19, expressed at all stages of B cell differentiation, presents an opportunity for CAR-T cell therapy in ITP. This study aims to evaluate the efficacy of CD19 CAR-T cell immunotherapy in an active murine ITP model.

Methods: CD42-knockout mice were immunized with wild type (WT) C57BL/6 mice and splenocytes from these immunized mice were transplanted into irradiated WT mice to construct a murine model of active ITP. The ITP mice were then randomized into two groups, with the experimental group receiving an intraperitoneal injection with 1×106 CD19 CAR-T cells. Platelet counts were monitored weekly, and after 3 weeks, the ITP mice were euthanized and sacrificed. Single-cell suspensions were prepared from harvested spleens for analysis. Anti-murine antibodies were analyzed using flow cytometry (Beckmann Coulter, Brea, CA, USA). All data were analyzed by Statistical Package for the Social Sciences (SPSS) software, version 25.0 (IBM Corp., Armonk, NY, USA). P < 0.05 was considered statistically significance.

Results: Our results demonstrated that the platelet counts of ITP mice reached their lowest level on day 7 after spleen cell transplantation, gradually recovering within a week. Platelet counts were significantly higher in the CD19 CAR-T cell therapy group compared to the control group on day 7 and persisted until day 21. There were no significant differences in weight between two groups, indicating no severe complication or CRS were identified. In the third week CD19 CAR-T cell therapy, the proportion of plasma cells in the spleen was determined, showing a marked decrease in the percentage of CD138+ plasma cells in the CAR-T group compared to the control group. Additionally, at day 14, the titers of anti-platelet CD42-specific antibodies were significantly lower in the CAR-T cell treated group compared to the control group. Furthermore, the mean fluorescence intensity (MFI) of CD19+ B cells in the spleen cells of the CD19 CAR-T cell immunotherapy group was significantly decreased compared to the control group.

Conclusion: This study demonstrates the effectiveness of CD19 CAR-T cell therapy in treating thrombocytopenia by suppressing plasma and B cells in a mouse model of active ITP. These findings provide valuable insights into the potential therapeutic application of CD19 CAR-T cell immunotherapy for immune thrombocytopenia.

Disclosure: No conflict of interest.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH