FIELD: biotechnology.
SUBSTANCE: modified replicating adenovirus of serotype 5, having lytic activity in cancer target cells, is proposed, containing: a) deletion of E1A gene, while the specified deletion is deletion of base pairs 923-946; b) chimeric substitution of 5/3 of a protrusion of adenovirus fiber protein, while the specified protrusion of serotype 5 Ad is substituted with a protrusion of serotype 3 Ad; c) deletion of 14.7k gene, while the specified deletion is deletion of base pairs 30,448-30,834 compared to a wild-type adenovirus, and a sequence of C-end of RID beta GGA GGA GAT GAC TGA gene is substituted with GGA GGA GAC GAC TGA; and d) deletion of gp19k gene and deletion of 7.1k gene, while the specified deletions are deletions of base pairs 28,541-29,211 compared to the wild-type adenovirus. A pharmaceutical composition is proposed, containing at least one modified adenovirus competent for replication, showing lytic activity against a target cell. The use of at least one modified adenovirus competent for replication, showing lytic activity against a target cell, or a pharmaceutical composition in the production of a drug for the treatment of cancer is proposed. A method for the treatment of cancer in a patient is proposed, including administration to the patient of effective amount of a pharmaceutical composition or a composition containing at least one modified adenovirus competent for replication, showing lytic activity against a target cell.
EFFECT: claimed invention solves the problem of immunosuppression in the tumor environment, since the presence of a highly immunogenic oncolytic adenovirus encoding human immune-stimulating transgenes forms the tumor microenvironment towards an “immuno-inflammatory” phenotype, which is more susceptible to immunotherapeutic approaches.
22 cl, 10 dwg, 5 tbl
