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Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently

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Abstract

CD19 chimeric antigen receptor (CAR) T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia (R/R ALL), but compromising result in chronic lymphoblastic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL). CD19 relapse and the lack of CAR-T cell persistence which result in treatment failure are considerable obstacles to overcome. CAR-T targeting CD20 is an option for salvaging CD19 CAR-T failure. Previous studies have established variant structures of bispecific CAR-T which could avoid antigen-loss and immune escape. Here, we constructed tandem and loop CAR structures targeting both CD19 and CD20 antigen. Bispecific CAR-T cells could eliminate either CD19 or CD20 negative lymphoma cells, suggesting they exhibited dual antigen targeting of CD19 and CD20. By comparing the efficiency of four bispecific CAR modified T cells, it was found that loop2019 CAR was the best structure among them to eradicate lymphoma cell lines and patients’ primary lymphoma or CLL cells in a very low dose in vitro and prolong the survival time dramatically in lymphoma xenograft mice model. These data highlighted the potential of loop2019 CAR-T in clinical treatment.

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Acknowledgements

This work was supported by the National Key Research & Development Program of China (2019YFA0110200), the National Natural Science Foundation of China (81830005), the CAMS Innovation Fund for Medical Sciences (2021-I2M-1-041) and the Tianjin Applied Fundamental Research Planning Key Project (20JCZDJC00120).

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Authors and Affiliations

  1. State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China

    Zhaoqi Chen, Yan Liu, Nianci Chen, Haiyan Xing, Zheng Tian, Kejing Tang, Qing Rao, Yingxi Xu, Ying Wang, Min Wang & Jianxiang Wang

  2. National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China

    Ying Wang & Jianxiang Wang

  3. Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China

    Zhaoqi Chen, Yan Liu, Nianci Chen, Haiyan Xing, Zheng Tian, Kejing Tang, Qing Rao, Yingxi Xu, Min Wang & Jianxiang Wang

  4. Tianjin Key Laboratory of Cell Therapy for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China

    Zhaoqi Chen, Yan Liu, Nianci Chen, Haiyan Xing, Zheng Tian, Kejing Tang, Qing Rao, Yingxi Xu, Ying Wang, Min Wang & Jianxiang Wang

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  1. Zhaoqi Chen
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  2. Yan Liu
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  3. Nianci Chen
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  7. Qing Rao
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  8. Yingxi Xu
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  9. Ying Wang
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  10. Min Wang
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  11. Jianxiang Wang
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Correspondence to Min Wang or Jianxiang Wang.

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The supporting information is available online at https://doi.org/10.1007/s11427-022-2173-9. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

The author(s) declare that they have no conflict of interest. All human subjects and animals performed in this study were in accordance with the ethical standards of the 1975 Helsinki declaration, and that they followed out the policy concerning Informed Consent as shown on Springer.com

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Chen, Z., Liu, Y., Chen, N. et al. Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently. Sci. China Life Sci. 66, 754–770 (2023). https://doi.org/10.1007/s11427-022-2173-9

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