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ACUTE LYMPHOBLASTIC LEUKEMIA

CD7 targeted “off-the-shelf” CAR-T demonstrates robust in vivo expansion and high efficacy in the treatment of patients with relapsed and refractory T cell malignancies

Leukemia volume 37, pages 2176–2186 (2023)Cite this article

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Abstract

T-cell acute lymphoblastic leukemia (T-ALL) represents an area of highly unmet medical needs. Once relapsed, patients have limited treatment options and poor prognosis. T-ALL antigens such as CD7 is extensively expressed in normal T cells and natural killer (NK) cells, and extending the success of CAR-T therapy to T cell malignancies was challenged by CAR-T cell fratricide, high production cost, and potential product contaminations. GC027 is an “off-the-shelf” allogeneic CD7 targeted CAR-T therapeutic product for T cell malignancies. It demonstrated superior cell expansion and antileukemia efficacy in mouse xenograft model. In our previous study, we observed promising efficacy results in the first two relapsed and refractory(R/R) T-ALL patients treated with GC027. In the expanded study, 11 out of 12 patients had rapid eradication of T-lymphoblasts and reached complete response within 1-month after GC027 infusion. GC027 cells expanded quickly beginning at infusion and reached to peak around 5–10 days after infusion. For most patients with a response(9/11), GC027 could not be detected via flow cytometry or qPCR 4 weeks after infusion. One patient had progression free survival of >3 years. With manageable toxicity profile, GC027 demonstrated superior clinical efficacy to standard chemotherapy regimens in (R/R) T cell malignancies.

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Fig. 1: Schematic illustration of GC027 product design.
Fig. 2: In vitro characteristics of GC027.
Fig. 3: In vivo efficacy in a human T-ALL xenograft murine model.
Fig. 4: Trial design and patient enrollment flow chart.
Fig. 5: Safety and efficacy evaluations of patients with R/R T-ALL after GC027 treatment.
Fig. 6: Detection of GC027 and target cells.

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Data availability

All data included in this study are available upon request by contact with the corresponding author.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (No. 82100242), the Biomedical Major Project of Yunnan Province (No. 202102AA100011), the Basic Research Project of Yunnan Province(Youth program, No. 202101AU070090), the Young and Middle-aged Academic and Technical Leaders Reserve Talent Project of Yunnan Province (202205AC160074), the Application-review Project of 920th Hospital (No. 2020YGC01) and the Yunnan Applied Basic Research Projects-Union Foundation (No. 202201AY070001-280 and No. 202201AY070001-278).

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Author notes

  1. These authors contributed equally: Shiqi Li, Xinxin Wang, Lin Liu.

Authors and Affiliations

  1. 920th Hospital of Joint Logistics Support Force of People’s Liberation Army of China, Kunming, 650100, Yunnan, China

    Shiqi Li, Lin Liu, Zhongtao Yuan, Yu Li, Le Luo, Lihua Zhang, Lvzhe Chen, Ping Yin, Chunmin Li, Xiaoping Li, Youcheng Wang, Yancheng Dong, Dingsong Zhang, Qingying Zang, Yingnian Chen & Sanbin Wang

  2. Gracell Biotechnologies Co., Ltd, Shanghai, 200030, China

    Xinxin Wang, Jia Liu, Gui Li, Zhimin Li, Sheng Li, Jiaping He, Wenhui Huang, Lianjun Shen, Wenling Li & Wei Cao

  3. Xinqiao Hospital, Chongqing, 400037, China

    Jun Rao, Li Gao & Xi Zhang

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  1. Shiqi Li
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Contributions

SW and XZ designed and leaded the clinical trial; SL and LLiu provided patient care and analyzed data. SL and XW wrote the manuscript. WC and XW designed the CAR-T product and in vitro experiments, and interpreted preclinical data. LS supervised the preclinical experiments and data interpretation. SL and Wenhui Huang conducted the preclinical experiments and data analysis. JH supervised CAR-T production. ZY, LLuo and YL provided clinical assistance. JL, GL, and ZL coordinated the study and data interpretation. WL reviewed the data and manuscript. LC, and PY and conducted clinical experiments. LG, JR, LZ, CL, XL, YW, DZ and YD provided clinical support and analyzed clinical data. LF and YC provided nursing support.

Corresponding authors

Correspondence to Wei Cao, Xi Zhang or Sanbin Wang.

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Competing interests

Gracell conceived and designed the GC027 product, performed the preclinical studies, manufactured the product and coordinated the study. The authors declare no competing interests.

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Li, S., Wang, X., Liu, L. et al. CD7 targeted “off-the-shelf” CAR-T demonstrates robust in vivo expansion and high efficacy in the treatment of patients with relapsed and refractory T cell malignancies. Leukemia 37, 2176–2186 (2023). https://doi.org/10.1038/s41375-023-02018-4

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  • DOI: https://doi.org/10.1038/s41375-023-02018-4

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