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ACUTE MYELOID LEUKEMIA

Characteristics of anti-CLL1 based CAR-T therapy for children with relapsed or refractory acute myeloid leukemia: the multi-center efficacy and safety interim analysis

Leukemia volume 36, pages 2596–2604 (2022)Cite this article

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Abstract

C-type lectin-like molecule-1 (CLL1) is preferentially expressed on acute myeloid leukemia (AML) stem cells and AML blasts, which can be considered as AML-associated antigen. Anti-CLL1-based CAR-T cells exhibited effective tumor-killing capacity in vitro and in AML-bearing mouse model. In this report, eight children with relapsed or refractory AML (R/R-AML) were recruited for a phase 1/2 clinical trial of autologous anti-CLL1 CAR-T cell immunotherapy. The objectives of this clinical trial were to evaluate the safety and the preliminary efficacy of anti-CLL1 CAR-T cell treatment. Patients received one dose of autologous anti-CLL1 CAR-T cells after lymphodepletion conditioning. After CAR-T treatment, patients developed grade 1–2 cytokine release syndrome (CRS) but without any lethal events. 4 out of 8 patients achieved morphologic leukemia-free state (MLFS) and minimal residual disease (MRD) negativity, 1 patient with MLFS and MRD positivity, 1 patient achieved complete remission with incomplete hematologic recovery (CRi) but MRD positivity, 1 patient with partial remission (PR), and 1 patient remained at stable disease (SD) status but had CLL1-positive AML blast clearance. These results suggested that anti-CLL1-based CAR-T cell immunotherapy can be considered as a well-tolerated and effective option for treating children with R/R-AML.

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Fig. 1: Anti-CLL1 CAR-T showed strong anti-tumor activity in pre-clinical mouse model.
Fig. 2: Anti-CLL1 CAR-T induced complete remission in AML patients.

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All data generated or analyzed during this study are included in this published article and its supplementary information files. Further inquiries can be directed to the corresponding authors.

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Acknowledgements

We would like to thank all the patients and their parents for their participation. This work was sponsored by Natural Science Foundation of Xinjiang (NO.2021D01C351), and supported by Guangzhou Science & Technology Project (202206010141), and partially funded by research funds from St. Baldrick’s Foundation International Scholar (581580), Guangzhou Women and Children’s Medical Center Internal Program (IP-2018-001), and Pearl River S&T Nova Program of Guangzhou (201906010056).

Funding

This work was sponsored by Natural Science Foundation of Xinjiang (NO.2021D01C351), and supported by Guangzhou Science & Technology Project (202206010141), and partially funded by research funds from St. Baldrick’s Foundation International Scholar (581580), Guangzhou Women and Children’s Medical Center Internal Program (IP-2018-001), and Pearl River S&T Nova Program of Guangzhou (201906010056). This work was also partially supported by grant from National Natural Science Foundation of China (82170152).

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Author notes

  1. These authors contributed equally: Hui Zhang, Chaoke Bu, Zhiyong Peng, Guangchao Li.

Authors and Affiliations

  1. Department of Pediatric Hematology/Oncology, Guangzhou Women and Children’s Medical Center, Guangzhou, China

    Hui Zhang, Yingyi He, Zhengbin Hu & Kunlin Pei

  2. Department of Hematology/Oncology, Shanghai Jiaotong University School of Medicine Affiliated Shanghai Children’s Medical Center, Shanghai, China

    Hui Zhang

  3. Nanfang-Chunfu Children’s Institute of Hematology and Oncology, Taixin Hospital, Dongguan, China

    Chaoke Bu, Zhiyong Peng & Chunfu Li

  4. Guangzhou Bio-Gene Technology Co., Ltd, Guangzhou, China

    Guangchao Li, Zhao Zhou, Wen Ding, Yongwei Zheng & Min Luo

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Contributions

The study was conceived by HZ and CL, designed by HZ, CL, and ML, supervised by HZ, CL, and ML. HZ, CB, ZP, GL and CL performed the research. HZ, CB, ZP, YH, ZH, and KP recruited the patients and collected clinical data. Data was conducted and interpreted by HZ, CB, ZP, GL, ZZ, WD, ML and CL. HZ, CL, YZ and ML wrote the manuscript. All authors approved the final version for publication.

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Correspondence to Min Luo or Chunfu Li.

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Competing interests

GL, ZZ, WD, YZ and ML are employees of Guangzhou Bio-Gene Technology Co., Ltd., who have potential interest, while other authors have nothing to disclose.

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Zhang, H., Bu, C., Peng, Z. et al. Characteristics of anti-CLL1 based CAR-T therapy for children with relapsed or refractory acute myeloid leukemia: the multi-center efficacy and safety interim analysis. Leukemia 36, 2596–2604 (2022). https://doi.org/10.1038/s41375-022-01703-0

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