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

• Published in: Blood cancer journal (New York) 2021-08, Vol.11 (8), p.144-144, Article 144
• Main Authors: Chen, Nianci, Xu, Yingxi, Mou, Junli, Rao, Qing, Xing, Haiyan, Tian, Zheng, Tang, Kejing, Wang, Min, Wang, Jiangxiang
• Format: Article
• Language: English
• Subjects: 13; 14/5; 14/63; 631/250/251; 631/67/1059; 96/31; Animals; Antigens; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Proliferation; Hematology; Humans; Immunotherapy, Adoptive - methods; Leukemia; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - pathology; Leukemia, Myeloid, Acute - therapy; Lymphocytes; Medical prognosis; Mice; Oncology; Prognosis; Receptors, Chimeric Antigen - therapeutic use; Receptors, Interleukin-10 - analysis; Receptors, Interleukin-10 - antagonists & inhibitors
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/s41408-021-00536-x

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.