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Bispecific BCMA/CD19 targeted CAR-T cell therapy forces sustained disappearance of symptoms and anti-acetylcholine receptor antibodies in refractory myasthenia gravis: a case report

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Fig. 1
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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We are grateful to the patient and relatives for their collaborations.

Funding

This work was funded by The Medical research project of Jiangsu Provincial Health Commission (M2022118), The Natural Science Foundation of Jiangsu Province (BK20231158), National Natural Science Foundation of China (81972719, 82273207).

Author information

Author notes

  1. Yong Zhang, Dan Liu and Zhouao Zhang have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China

    Yong Zhang, Zhouao Zhang, **aoyu Huang, Xue Du, Zhouyi Wang, Ming** Yang, Tiancheng Luo, Sha liu, Wan Zhang, Ying Sheng, Wei Zhang, Hao Chen, Shenyang Zhang, **aopeng Wang, Wenqing Meng & Guiyun Cui

  2. Cancer Institute, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China

    Dan Liu, Gang Wang, Huizhong Li & Ming Shi

  3. Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China

    Dan Liu, Gang Wang, Huizhong Li & Ming Shi

  4. Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China

    Dan Liu, Gang Wang, Huizhong Li, Ming Shi & Junnian Zheng

  5. Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China

    Jiang Cao

  6. Neuroimmunology Group, KingMed Diagnostic Laboratory, Guangzhou, China

    Shenghua Zong

Authors
  1. Yong Zhang
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  2. Dan Liu
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  3. Zhouao Zhang
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  4. **aoyu Huang
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  5. Jiang Cao
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  7. Xue Du
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  8. Zhouyi Wang
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  9. Ming** Yang
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  10. Tiancheng Luo
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  12. Wan Zhang
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  15. Wei Zhang
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  17. Shenyang Zhang
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  18. **aopeng Wang
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  19. Wenqing Meng
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  20. Shenghua Zong
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  21. Ming Shi
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  22. Junnian Zheng
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  23. Guiyun Cui
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Contributions

GYC, JNZ, MS, YZ, and JC were responsible for the study protocol design and conceptualization. ZAZ, GW, XD, ZYW, MJY, TCL, SL, ZHL, WZ, SYZ, XPW, and WQM contribute to data collection and analysis. ZAZ, WZ, YS, and HC are responsible for follow-up. YZ, DL, ZAZ, MS, and XYH contributed to writing the first draft. SHZ contributed to detecting the titers of serum anti-AChR antibodies. All authors were involved at each stage of manuscript preparation and approved the final version.

Corresponding authors

Correspondence to Ming Shi, Junnian Zheng or Guiyun Cui.

Ethics declarations

Conflicts of interest

The authors declare no conflict of interest.

Ethical standard

The study was approved by the Ethics Committee of the Affiliated Hospital of Xuzhou Medical University (XYFY2022-KL057-02, ChiCTR2200061267). All investigations were carried out according to the Declaration of Helsinki. Patient consent for publication was obtained. The patients gave explicit informed consent to report their clinical cases.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 2762 KB)

Fig. S1

In Supplementary Materials: The bispecific anti-BCMA/CD19 CAR-T cells construct. The secondary generation CAR construction containing the bispecific tandem single-chain variable fragments, CD8 α Hinge and transmembrane domains, 4-1BB co-stimulatory domains, and CD3 ξ Activation domain. Abbreviations: BCMA B-cell maturation antigen, Bs bispecific, CAR chimeric antigen receptor, TM transmembrane (TIF 3090 KB)

Fig. S2

In Supplementary Materials: T-cell subsets and cytokines changes following CAR T-cell infusion. a–d Changes of CD3 + T cells, CD4 + T cells, CD8 + T cells, and NK cells after CAR T-cell infusion. e–o Changes of cytokines including IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-17, IFN-α, IFN-γ, and TNF-α after CAR-T cells infusion. Abbreviations: CAR chimeric antigen receptor, IFN interferon, IL interleukin, NK natural killer, TNF tumor necrosis factor (TIF 1179 KB)

Fig. S3

In Supplementary Materials: Temperature and serological changes following CAR T-cell infusion. (Grey area indicates the reference range. Red arrow indicates the time of CAR T-cell infusion) a The changes of temperature in the whole course; b–f Counts of WBC, neutrophil, lymphocyte, RBC, and platelet; g–j Serum levels of hemoglobin, AST, ALT, and albumin. Abbreviations: AST aspartate aminotransferase, ALT alanine aminotransferase, CAR chimeric antigen receptor, RBC red blood cell, WBC white blood cell (TIF 2006 KB)

Fig. S4

In Supplementary Materials: The expansion of anti- BCMA/CD19 bispecific CAR-T cells in vivo, and changes of B cells, immunoglobulin, and interleukin-6 of the patient. a CAR-T cells expansion was tested by determining CAR gene copy number in peripheral blood; b The circulating CD19 + B cells before and after CAR-T cells infusion were determined by flow cytometry; c–f The changes of serum IgG, IgM, IgA, and interleukin-6. Abbreviations: BCMA B-cell maturation antigen, BL baseline, CAR chimeric antigen receptor, Ig immunoglobulin (TIF 1082 KB)

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Zhang, Y., Liu, D., Zhang, Z. et al. Bispecific BCMA/CD19 targeted CAR-T cell therapy forces sustained disappearance of symptoms and anti-acetylcholine receptor antibodies in refractory myasthenia gravis: a case report. J Neurol 271, 4655–4659 (2024). https://doi.org/10.1007/s00415-024-12367-4

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  • DOI: https://doi.org/10.1007/s00415-024-12367-4

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