T CELLS RE-TARGETED WITH RESPECT TO CD123-SPECIFIC CHIMERIC ANTIGEN RECEPTOR, AND METHODS FOR USE THEREOF Russian patent published in 2020 - IPC C07K14/705 C12N5/783 C12N5/10 A61K35/17 A61P35/00 

FIELD: biotechnology.

SUBSTANCE: invention relates to the field of biotechnology, specifically to chimeric antigenic receptors aimed at CD123 (CD123CAR). Constructing a nucleic acid molecule encoding CD123CAR, including: anti-CD123-scFv-region; a hinge region of IgG4 with SEQ ID NO: 13 with N79Q and L17E replacements and optionally S10P; transmembrane domain; costimulatory signal domain CD27, CD28, 4-1BB or OX40; and the T-cell receptor zeta chain signal domain. When T-cells (CD4/CD8) from normal CD123CAR donors are expressed, T-cell specificity is re-targeted and powerful effector activity is mediated in relation to CD123 cell lines⁺, as well as primary samples from AML patients. Besides, T-cells obtained from patients with active AML can be modified for expression of CD123CAR genes and capable of lysing autologous AML-blasts in vitro. Finally, one dose 5.0 × 10⁶ CAR123-T-cells results in considerable delay of leukaemia progression in mice that allows using CD123CAR-transduced T-cells in immunotherapy for treating high AML risk.

EFFECT: invention can be used in medicine for treating acute myeloid leukemia (AML).

22 cl, 16 dwg, 1 tbl, 2 ex