Противоопухолевый потенциал рекомбинантного штамма вируса осповакцины, продуцирующего секретируемый химерный белок, состоящий из ГМ-КСФ человека и онкотоксического белка лактаптина

Recombinant VV-GMCSF/lact-dGF was constructed using L-IVP strain of vaccinia virus (VACV). The recombinant strain possesses deletions of gene fragments of viral thymidine kinase and growth factor, and insertion of chimeric peptide GMCSF/lact into region of thymidine kinase gene deletion. The transgene includes gene adjuvant GM-CSF connected with oncotoxic peptide lactaptin by flexible linker GlyGlyGlySer. The transgene expresses under control of natural promoter P7.5k of VACV and produces a secreted form of chimera protein GMCSF/lact (46 kDa), which have biological activity of GM-CSF and lactaptin. Strain VV-GMCSF/lact-dGF demonstrated highly targeted oncolytic activity toward human tumor cells of various origination. Single injection of the VV-GMCSF/lact – dGF strain in a dose 10 7 PFU/mouse into xenografts of human breast cancer BT-549 cells in nude mice results in complete destruction of tumor tissue and its infiltration by effector cells of immune system. The strain VV-GMCSF/lact – dGF looks promising for elaboration of a preparation for malignancies treatment, and further studies of the mechanisms of its antitumor activity are reasonable.