CD147-specific chimeric antigen receptor T cells effectively inhibit T cell acute lymphoblastic leukemia.

Journal: Cancer letters
PMID: 35659513

Abstract

T cell acute lymphoblastic leukemia (T-ALL) is invasive and heterogeneous, and existing therapies are sometimes unsuccessful. Chimeric antigen receptor (CAR) T cell therapy is a breakthrough tumor treatment method, particularly for B cell acute lymphoblastic leukemia. We found that CD147 was highly expressed in tumor T cells of T-ALL patients and T cell lymphoma. Therefore, CD147-CAR T cells that contain a humanized single-chain variable fragment targeting human CD147 and a second-generation CAR frame were constructed for treating T-ALL. CD147-CAR T cells were able to maintain a healthy proliferation rate, preserving a subset of CD62L+/CCR7+ memory T cells. CD147-CAR T cells showed a potent anti-tumor activity against human T-ALL cell line and T-ALL blasts, releasing high level of cytokines in the process. However, CD147-CAR T cells exhibited potential safety toward human normal cells and CD147-deficent cells. NOD/ShiLtJGpt-PrkdcIl2rg/Gpt mice were used to establish a T-ALL xenograft model and CD147-CAR T cells conferred robust protection against T-ALL progression and significantly improved survival in mice. Overall, we found that CD147 is a potential antigen target of CAR T cell therapy for T-ALL.

Authors

  • Nai-Shan Zheng
    National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Xiang-Yu Zhao
    Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.
  • Ding Wei
    National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Jin-Lin Miao
    National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Ze-Kun Liu
    National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Yu-Le Yong
    National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Ren-Yu Zhang
    National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Yi-Xiao Guo
    National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Lin He
    College of Plant Protection, Southwest University, Chongqing, China.
  • Bin Wang
    State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau, Northwest A&F University, Yangling 712100, China; New South Wales Department of Primary Industries, Wagga Wagga Agricultural Institute, Wagga Wagga 2650, Australia. Electronic address: bin.a.wang@dpi.nsw.gov.au.
  • Xiu-Xuan Sun
    National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Hai-Jiao Yang
    National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Tian-Jiao Zhang
    National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Qian He
    National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Xiao-Min Li
    National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Hai Zhang
    a State Key Laboratory Breeding Base of Systematic Research Development and Utilization of Chinese Medicine Resources, Sichuan Province and Ministry of Science and Technology, College of Pharmacy and College of Ethnic Medicine , Chengdu University of Traditional Chinese Medicine , Chengdu , China.
  • Rong Hou
    National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China.
  • Peng Lin
    Zhejiang Key Laboratory of Excited-State Energy Conversion and Energy Storage, Department of Chemistry, Zhejiang University, Hangzhou 310058, China.
  • Ying-Ming Xu
    Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
  • Xiao-jun Huang
  • Zhi-Nan Chen
    National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China. Electronic address: znchen@fmmu.edu.cn.
  • Huijie Bian
    National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, 710032, China. Electronic address: hjbian@fmmu.edu.cn.

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