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Quantitative characterization of T-cell repertoire alteration in Chinese patients with B-cell acute lymphocyte leukemia after CAR-T therapy

Bone Marrow Transplantation volume 54, pages 2072–2080 (2019)Cite this article

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Abstract

Chimeric antigen receptor (CAR) T-cell therapy has displayed potent anti-leukemia activity in acute lymphocytic leukemia (ALL), acting as a new ray of hope to refractory/relapsed patients. However, the influence of CAR-T therapy on host immune system has not been well elucidated. Thus, We applied high-throughput T cell receptor β chain sequencing to track the dynamic change of T-cell repertoire induced by CAR-T therapy in B-cell ALL patients. Six Chinese patients achieving complete remission were under observation, whose blood samples, bone marrow samples and infused CAR-T samples were collected at serial time points before and after CAR-T therapy. We observed decreased TCR diversity and increased clonality of T-cell repertoire in both peripheral blood and bone marrow after CAR-T administration. The persistent T cell clones in blood and bone marrow expanded following leukemic cell destruction and were barely detected in CAR T-cell pool. For the first time, our results demonstrated CAR-T therapy could stimulate the clonal proliferation of CAR-negative T cells in patients. Considering other groups’ animal results indicating that CAR-T therapy could facilitate the proliferation of tumor antigen-specific T cells and that the emergence of these T cell clones followed the destruction of leukemic cells, they are most likely tumor antigen-specific.

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Acknowledgements

The authors thank the patients and families for their participation in this study and the help of nurse team on patients’ care and sample collection. Finally, thank the grant supported by the National Key Basic Research Program of China (2015CB964900), National Key Nature Science Foundation of China (81730008), Key Project of Science and Technology Department of Zhejiang Province (2015C03038; 2018C030162), and National Nature Science Foundation of China (81770201).

Funding

This work was supported by the National Key Basic Research Program of China (2015CB964900), National Key Nature Science Foundation of China (81730008), Key Project of Science and Technology Department of Zhejiang Province (2015C03038; 2018C030162), and National Nature Science Foundation of China (81770201).

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  1. These authors contributed equally: Xiujian Wang, Yongxian Hu, Xiao Liu

Authors and Affiliations

  1. Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Xiujian Wang, Yongxian Hu, Jian Yu, Guoqing Wei, Wenjun Wu, Huarui Fu, Lijuan Ding, Fang Ni, Hao Zhang, Zuyu Liang, Binsheng Wang, Xiaoqing Li, Cong Wei, Jimin Shi & He Huang

  2. Institute of Hematology, Zhejiang University, Hangzhou, China

    Xiujian Wang, Yongxian Hu, Jian Yu, Guoqing Wei, Wenjun Wu, Huarui Fu, Lijuan Ding, Fang Ni, Hao Zhang, Zuyu Liang, Binsheng Wang, Xiaoqing Li, Cong Wei, Jimin Shi & He Huang

  3. Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China

    Xiujian Wang, Yongxian Hu, Jian Yu, Guoqing Wei, Wenjun Wu, Huarui Fu, Lijuan Ding, Fang Ni, Hao Zhang, Zuyu Liang, Binsheng Wang, Xiaoqing Li, Cong Wei, Jimin Shi & He Huang

  4. Stem Cell Institute, Zhejiang University, Hangzhou, China

    Xiujian Wang, Yongxian Hu, Jian Yu, Guoqing Wei, Wenjun Wu, Huarui Fu, Lijuan Ding, Fang Ni, Hao Zhang, Zuyu Liang, Binsheng Wang, Xiaoqing Li, Cong Wei, Jimin Shi & He Huang

  5. Department of Human Genetics, The University of Chicago, Chicago, IL, USA

    Xiao Liu

  6. Hangzhou ImmuQuad Biotechnologies, LLC, Hangzhou, China

    Pengfei Xu, Chao Jin, Yunyun Deng & Tao Sun

  7. Innovative Cellular Therapeutics Co, Ltd (formerly SiDanSai Biotechnology Co,12 Ltd), Shanghai, China

    Lei Xiao & Zhao Wu

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  1. Xiujian Wang
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Correspondence to Tao Sun or He Huang.

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Wang, X., Hu, Y., Liu, X. et al. Quantitative characterization of T-cell repertoire alteration in Chinese patients with B-cell acute lymphocyte leukemia after CAR-T therapy. Bone Marrow Transplant 54, 2072–2080 (2019). https://doi.org/10.1038/s41409-019-0625-y

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