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Immunotherapy

Unique CDR3 epitope targeting by CAR-T cells is a viable approach for treating T-cell malignancies

Leukemia volume 33, pages 2315–2319 (2019)Cite this article

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A Correction to this article was published on 16 May 2019

This article has been updated

Efficient and specific removal of malignant cells is the ultimate goal of cancer therapy. The current rapid development of chimeric antigen receptor T-cell (CAR-T-cell or CART) therapy potentially provides high efficiency and allows long-term surveillance, which have greatly extended the frontier of leukemia treatment.

We collected pathological samples from nine leukemia patients (four with T-cell acute lymphoblastic leukemia (T-ALL) and 5 with T-cell non-Hodgkin lymphoma (T-NHL), Supplementary Table S1) pathologically confirmed by histology and flow cytometry, and four healthy donors (normal controls) to study TCR diversity. Isolated cells (as well as Jurkat and MOLT-4 cells as controls) were used for gDNA extraction, amplification of the CDR3 region of TCRβ chain sequences and NGS analysis (Supplementary Fig. S1, Table S2). Consistent with previous reports [13], the TCR diversity of T-cells from leukemia patients showed an abnormal predominance of CDR3 sequences (the frequency ranged from 7 to 94%), while no single clone exhibited a frequency of higher than 2% in T-cells from healthy donors (Fig. 1b). Identified dominant, unique CDR3 sequences from the leukemia, Jurkat and MOLT-4 cells were chemically synthesized and used for further applications.

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Fig. 1
Fig. 2

Change history

  • 16 May 2019

    In the original version of this article the author name Xiaolei Chen was published incorrectly. This has been corrected to Xiao Lei Chen.

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Acknowledgements

This work was supported by the Fujian Provincial Natural Science Foundation 2016S016 China and Putian city Natural Science Foundation 2014S06(2), Fujian Province, China. Alexey Stepanov and Alexander Gabibov were supported by Russian Scientific Foundation project No. 17-74-30019. Jinqi Huang was supported by a doctoral fellowship from Xiamen University, China.

Author Contributions

JH, SA, JL, GF, XC, and CMT designed the study; JH, SA, JL, JXJZ, and XX performed and analyzed the experiments; JH, DC, and XW contributed to patient clinical care and data collection; JX and GF provided scientific advice; TJ, GG, and LD proof read the manuscript, JH, SA, JL, GF, MM, AG, JX, and CMT wrote the paper; and all authors read and approved the final version of the manuscript.

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Author notes

  1. These authors contributed equally: Jinqi Huang, Stepanov Alexey, Jian Li

Authors and Affiliations

  1. Translational Medicine Research Center (TMRC), School of Pharmaceutical Sciences, Xiamen University, Xiamen, China

    Jinqi Huang & Chi-Meng Tzeng

  2. Department of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA

    Jinqi Huang, Terri Jones, Geramie Grande, Lacey Douthit & Jia Xie

  3. M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16 /10, Moscow, 117997, Russia

    Stepanov Alexey & Gabibov Alexander

  4. State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China

    Jian Li, Jun Xie, Changchun Xiao, Xiao Lei Chen & Guo Fu

  5. The Affiliated Hospital of Putian University, Putian, Fujian, China

    Danna Chen

  6. ProteinT Biotechnology Ltd. Co. Tianjin Airport Free Trade Zone, Tianjin, China

    Xiaolei Wu

  7. Dmitrii Rogachev Federal Research Center for Pediatric Hematology, Oncology and Immunology, Samory Mashela Str. 1, Moscow, 117997, Russia

    Maschan Michael

  8. Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA

    Changchun Xiao

  9. Department of Hematology, zhongshan Hospital of Xiamen University, Xiamen, 361004, Fujian, China

    Jiangning Zhao

  10. Department of Oncology, The first hospital of Putian City, Putian, 351100, Fujian, China

    Xuehua Xie

  11. School of Pharmacology, Nanjing Tech University, Nanjing, China

    Chi-Meng Tzeng

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  1. Jinqi Huang
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Corresponding authors

Correspondence to Xiao Lei Chen, Guo Fu, Gabibov Alexander or Chi-Meng Tzeng.

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Huang, J., Alexey, S., Li, J. et al. Unique CDR3 epitope targeting by CAR-T cells is a viable approach for treating T-cell malignancies. Leukemia 33, 2315–2319 (2019). https://doi.org/10.1038/s41375-019-0455-3

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