FIELD: biotechnology, medicine, oncology.
SUBSTANCE: invention can be used for the treatment of various tumor diseases. A hybrid protein molecule SRH-DR5-B containing at the N-terminus an angiogenesis-inhibiting peptide that specifically binds to VEGFR2, and at the C-terminus, a receptor-selective variant of the antitumor cytokine TRAIL DR5-B, which specifically binds to the death receptor DR5 are proposed. In another version of the fusion protein (SRH-DR5-B-iRGD), the C-terminus of the SRH-DR5-B protein contains a peptide that specifically binds to integrin 
followed by proteolytic cleavage and acquisition of affinity for the NRP-1 receptor. These hybrid proteins cause apoptotic death of tumor cells and inhibit angiogenesis in the tumor microenvironment.
EFFECT: in the case of SRH-DR5-B-iRGD, it also provides faster tumor accumulation and increased efficacy compared to the DR5-specific mutant variant of the antitumor cytokine TRAIL.
9 cl, 5 ex
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| GENETIC CASSETTE CONTAINING CODON-OPTIMIZED NUCLEOTIDE SEQUENCES OF TRAIL, PTEN AND IFNβ-1 GENES, AND PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF ONCOLOGIC DISEASES | 2020 |
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