FIELD: biotechnology.
SUBSTANCE: present invention relates to biotechnology, specifically to cell technologies, and can be used in medicine for cancer immunotherapy. Ex-vivo method for producing clofarabine and / or fludarabine-resistant T-cells involves the steps of: (a) transfecting T cells with a nucleotide sequence encoding a low-boiling endonuclease, specifically directed to a gene expressing an enzyme having deoxycytidine kinase activity (dcK – EC 2.7.1.74); (b) expressing said endonuclease in said T-cells to achieve targeted inactivation of said dcK gene; (c) propagation of said engineered T-cells obtained in step (b), optionally in the presence of clofarabine and / or fludarabine. Said T-cells represent allogenic T-cells from the donor, in which the gene coding the T-cell receptor component (RTL), which is selected from RTL alpha and RTL beta, is inactivated, or are autologous T-cells from the patient diagnosed with cancer; and wherein said cells express a chimeric receptor antigen (CAR) specific to the cancer antigen.
EFFECT: invention provides higher effectiveness of antineoplastic immunotherapy.
18 cl, 27 dwg, 4 ex
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Authors
Dates
2019-05-28—Published
2014-11-21—Filed