FIELD: biotechnology.
SUBSTANCE: mutant of lymphocytic choriomeningitis virus with antitumor activity has been described. This mutant contains a nucleic acid encoding a glycoprotein, where at least Arg 185 is replaced by Trp and Ile 181 is replaced by Met, compared with a wild-type glycoprotein. The use of this mutant for the treatment of cancer and for the manufacture of a pharmaceutical composition for the treatment of cancer is also presented. A method of cancer treatment is described, including the introduction of an effective amount of the specified mutant. A pharmaceutical composition containing the specified mutant is described. A glycoprotein involved in the infection of a tumor cell with a virus is presented, where the specified glycoprotein (a) contains the Arg 185 → Trp mutation, compared to the wild-type glycoprotein sequence, where the glycoprotein contains an amino acid sequence having at least 95% sequence identity with the sequence selected from the group consisting of SEQ ID NO: 18, SEQ ID NO: 26, SEQ ID NO: 34, SEQ ID NO: 42 and SEQ ID NO: 50; or (b) contains the Ile 181 → Met mutation, compared to the wild-type glycoprotein sequence, where the glycoprotein contains an amino acid sequence having at least 99% sequence identity with the sequence given under SEQ ID NO: 58. Described the nucleic acid encoding the specified glycoprotein. A glycoprotein involved in infection of a tumor cell with a virus is also presented, where the glycoprotein contains, compared with the sequence of the glycoprotein of the lymphocytic choriomeningitis virus (LCMV) of the wild type, given under SEQ ID NO: 10, (a) the Arg 185 → Trp mutation, where the glycoprotein contains an amino acid sequence having at least 95% sequence identity with a wild-type glycoprotein sequence given under SEQ ID NO: 10; or (b) the Ile 181 → Met mutation, where the glycoprotein contains an amino acid sequence having at least 99% of the sequence identity with the sequence given under SEQ ID NO: 10. A nucleic acid is presented for the expression of the specified glycoprotein. A gene cluster, an operon, and an expression vector for the expression of the specified glycoprotein containing the above nucleic acid are presented. A host cell for the expression of lymphocytic choriomeningitis virus expressing or containing glycoprotein and/or containing nucleic acid, as described above, is described. A virus with antitumor activity, expressing or containing glycoprotein and/or containing nucleic acid.
EFFECT: invention expands the arsenal of drugs for the treatment of cancer.
31 cl, 26 dwg
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Authors
Dates
2024-01-22—Published
2019-09-12—Filed