FIELD: biotechnology.
SUBSTANCE: invention relates to engineered natural killer (NK) cells expressing a chimeric receptor, and can be used in medicine for the treatment of cancer expressing natural killer receptor group 2 member D (NKG2D) ligand. The following is proposed: a chimeric receptor that binds NKG2D and contains the following amino acid sequence SEQ ID NO: 109, which includes an NKG2D fragment that binds native NKG2D ligands as an extracellular receptor domain, as well as an effector domain containing CD8a transmembrane domain, OX40 domain, and CD3-zeta. This chimeric receptor may be incorporated into a polypeptide proposed to enhance NK cell cytotoxicity that also contains membrane-bound interleukin 15 (mbIL15) with the following SEQ ID NO: 17.
EFFECT: invention makes it possible to obtain a chimeric receptor capable of transmitting a stimulating signal in an NK cell after binding to native NKG2D ligands, which provides unexpectedly increased cytotoxicity compared to unengineered NK cells.
19 cl, 28 dwg, 4 ex
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Authors
Dates
2024-11-21—Published
2018-03-27—Filed