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Immunotherapy

T cells redirected against Igβ for the immunotherapy of B cell lymphoma

Leukemia volume 34, pages 821–830 (2020)Cite this article

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Abstract

CD19-redirected CAR-T immunotherapy has emerged as a promising strategy for treatment of B cell lymphoma, however, many patients often relapsed due to antigen loss. Therefore, it is urgently needed to explore other suitable antigens targeted by CAR-T cells to cure B cell lymphoma. Igβ is a component of the B cell receptor (BCR) complex, which is highly expressed on the surface of lymphoma cells. In this study, we engineered T cells to express anti-Igβ CAR with CD28 costimulatory signaling moiety and observed that Igβ-CAR T cells could efficiently recognize and eliminate Igβ+ lymphoma cells both in vitro and in two different lymphoma xenograft models. The specificity of Igβ-CAR T cells was further confirmed through wild type or mutated Igβ gene transduction together with Igβ-specific knockout in target cells. Of note, both the in vitro and in vivo effect of Igβ CAR-T cells was comparable with that of CD19 CAR-T cells. Importantly, Igβ CAR-T cells recognized and eradicated patient-derived lymphoma cells in the autologous setting. Lastly, the safety of anti-Igβ CAR-T cells could be further enhanced by introduction of the inducible caspase-9 suicide gene system. Collectively, Igβ-specific CAR-T cells may be a promising immunotherapeutic approach for B cell lymphoma.

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Acknowledgements

This work was supported by the grants from the National Key R&D Program of China (2017YFA0104502, 2016YFC0902800), National Natural Science Foundation of China (81770216, 81302046, 81730003, 81470346), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and Six Talent Peaks Project in Jiangsu Province (2015-WSN-020).

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Author notes

  1. These authors contributed equally: Dongpeng Jiang, Xiaopeng Tian

Authors and Affiliations

  1. Institute of Blood and Marrow Transplantation, Medical College of Soochow University, Jiangsu Institute of Hematology, The first Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, National Clinical Research Center for Hematologic Diseases, Soochow University, Suzhou, China

    Dongpeng Jiang, Xiaosen Bian, Tingting Zhu, Huimin Qin, Ruixi Zhang, Yang Xu, Depei Wu & Jianhong Chu

  2. Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China

    Xiaopeng Tian, Haiwen Huang & Jianhong Fu

  3. Department of General Surgery, The first Affiliated Hospital of Soochow University, Suzhou, China

    Zhansheng Pan

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  1. Dongpeng Jiang
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Contributions

JC and DW supervised the project, designed experiments, and wrote the manuscript; DJ and XT designed and performed experiments, analyzed data, and wrote the manuscript; TZ, XB, HQ, RZ, YX, HH, JF and ZP performed experiments and analyzed data.

Corresponding authors

Correspondence to Depei Wu or Jianhong Chu.

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A patent application partly based on this study has been submitted.

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Jiang, D., Tian, X., Bian, X. et al. T cells redirected against Igβ for the immunotherapy of B cell lymphoma. Leukemia 34, 821–830 (2020). https://doi.org/10.1038/s41375-019-0607-5

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