Genetically engineered vaccinia viruses

Abstract

The present invention provides a genetically recombinant vaccinia virus effective in preventing or treating cancer. Specifically, the present invention provides a recombinant vaccinia virus lacking functions of VGF and O1L and having a gene encoding B5R in which an SCR domain has been deleted. Specifically, the present invention provides a vaccinia virus comprising two polynucleotides, a polynucleotide encoding IL-7 and a polynucleotide encoding IL-12; a combination kit of two vaccinia viruses, a vaccinia virus comprising a polynucleotide encoding IL-7 and a vaccinia virus comprising a polynucleotide encoding IL-12; and use of the two vaccinia viruses in combination.

1 . A vaccinia virus lacking functions of vaccinia virus growth factor (VGF) and O1L and having a gene encoding B5R in which an SCR (short consensus repeat) domain has been deleted. 
     
     
         2 . The vaccinia virus according to  claim 1 , wherein the vaccinia virus has a gene encoding B5R in which SCR domains 1 to 4 have been deleted. 
     
     
         3 . The vaccinia virus according to  claim 2 , wherein the deletion of SCR domains 1 to 4 in B5R is deletion of a region corresponding to the amino acid sequence represented by SEQ ID NO: 24 in B5R. 
     
     
         4 . The vaccinia virus according to  claim 1 , wherein the gene encoding B5R in which an SCR domain has been deleted is a gene encoding a polypeptide comprising a signal peptide, a stalk, a transmembrane domain and a cytoplasmic tail of B5R. 
     
     
         5 . The vaccinia virus according to  claim 1 , wherein the B5R in which an SCR domain has been deleted consists of an amino acid sequence of B5R corresponding to the amino acid sequence of SEQ ID NO: 25. 
     
     
         6 . The vaccinia virus according to  claim 1 , wherein the vaccinia virus is an LC16mO strain. 
     
     
         7 . A pharmaceutical composition comprising a vaccinia virus according to  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         8 . The pharmaceutical composition according to  claim 7 , wherein the pharmaceutical composition is for prevention or treatment of a cancer. 
     
     
         9 . The vaccinia virus according to  claim 2 , wherein the gene encoding B5R in which an SCR domain has been deleted is a gene encoding a polypeptide comprising a signal peptide, a stalk, a transmembrane domain and a cytoplasmic tail of B5R. 
     
     
         10 . The vaccinia virus according to  claim 2 , wherein the B5R in which an SCR domain has been deleted consists of an amino acid sequence of B5R corresponding to the amino acid sequence of SEQ ID NO: 25. 
     
     
         11 . The vaccinia virus according to  claim 2 , wherein the vaccinia virus is an LC16mO strain. 
     
     
         12 . The pharmaceutical composition comprising a vaccinia virus according to  claim 2 , and a pharmaceutically acceptable excipient. 
     
     
         13 . The vaccinia virus according to  claim 4 , wherein the B5R in which an SCR domain has been deleted consists of an amino acid sequence of B5R corresponding to the amino acid sequence of SEQ ID NO: 25. 
     
     
         14 . The vaccinia virus according to  claim 4 , wherein the vaccinia virus is an LC16mO strain. 
     
     
         15 . A pharmaceutical composition comprising the vaccinia virus according to  claim 4 , and a pharmaceutically acceptable excipient. 
     
     
         16 . A pharmaceutical composition comprising the vaccinia virus according to  claim 6 , and a pharmaceutically acceptable excipient. 
     
     
         17 . A method of treating cancer comprising administering the vaccinia virus according to  claim 1  to a subject with cancer. 
     
     
         18 . The method according to  claim 17 , wherein the cancer is selected from the group consisting of malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer, and gastric cancer. 
     
     
         19 . A method of treating cancer comprising administering the vaccinia virus according to  claim 6  to a subject with cancer. 
     
     
         20 . The method according to  claim 19 , wherein the cancer is selected from the group consisting of malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer, and gastric cancer.