2. Academic Validation
  3. Targeting of IL-10R on acute myeloid leukemia blasts with chimeric antigen receptor-expressing T cells

Targeting of IL-10R on acute myeloid leukemia blasts with chimeric antigen receptor-expressing T cells

  • Blood Cancer J. 2021 Aug 14;11(8):144. doi: 10.1038/s41408-021-00536-x.
Nianci Chen  # 1 2,  Yingxi Xu  # 1 2,  Junli Mou 1 2,  Qing Rao 1 2,  Haiyan Xing 1 2,  Zheng Tian 1 2,  Kejing Tang 1 2,  Min Wang 3 4,  Jiangxiang Wang 5 6 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
  • 2 Tianjin Key Laboratory of Cell Therapy for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
  • 3 State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. wangjxm@ihcams.ac.cn.
  • 4 Tianjin Key Laboratory of Cell Therapy for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. wangjxm@ihcams.ac.cn.
  • 5 State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. wangjx@ihcams.ac.cn.
  • 6 Tianjin Key Laboratory of Cell Therapy for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. wangjx@ihcams.ac.cn.
  • 7 National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. wangjx@ihcams.ac.cn.
  • # Contributed equally.
PMID: 34392305 DOI: 10.1038/s41408-021-00536-x
Abstract

Acute myeloid leukemia (AML) is a biologically and clinically heterogeneous disease with a dismal prognosis and limited treatment options. Chimeric antigen receptor (CAR) T cells have achieved unprecedented clinical responses in patients with B cell malignancies but a dismal consequences in AML. In our previous study, we found that interleukin-10 receptor (IL-10R) was overexpressed in most AML cells, and played an important role in promoting the stemness of leukemia cells. In this study, we developed a novel ligand-based CAR-T cell targeting IL-10R, which displayed striking cytotoxicity both in vitro and in vivo against AML cells. Except for monocytes, it had no significant adverse effects on the normal hematopoietic system, including CD34+ hematopoietic stem and progenitor cells (HSPCs). In addition, even though the incorporation of IL-10 in the CAR cassette led to phenotypes change, it had few adverse effects on the survival and biological activity of IL-10 CAR-T cells and did not cause excessive proliferation of leukemia cells. Therefore, we propose IL-10R is a novel promising therapeutic candidate for AML, and IL-10R targeted CAR-T therapy provides a new treatment strategy to improve the prognosis of AML.

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