Therapeutic agents comprising oncolytic vaccinia viruses and nk cells, and uses thereof for drugs for treatment of tumors and/or cancers

Abstract

The present disclosure provides therapeutic agents comprising oncolytic vaccinia viruses and NK cells, and uses thereof for preparation of drugs for treatment of tumors and/or cancers. The active ingredients of the therapeutic agents comprise an oncolytic vaccinia virus and NK cells, wherein the oncolytic vaccinia virus can selectively replicate in tumor cells.

What is claimed is: 
     
         1 . A therapeutic agent, comprising:
 (a) a first pharmaceutical composition comprising an oncolytic vaccinia virus in a first pharmaceutically acceptable carrier; and   (b) a second pharmaceutical composition comprising NK cells in a second pharmaceutically acceptable carrier;   wherein the oncolytic vaccinia virus can selectively replicate in tumor cells.   
     
     
         2 . The therapeutic agent of  claim 1 , wherein the first pharmaceutical composition and the second pharmaceutical composition are present separately in the therapeutic agent without being mixed together. 
     
     
         3 . The therapeutic agent of  claim 1 , wherein the active ingredient of the first pharmaceutical composition is the oncolytic vaccinia virus; and wherein the active ingredient of the second pharmaceutical composition is the NK cells. 
     
     
         4 . The therapeutic agent of  claim 1 , wherein the first pharmaceutical composition comprises the oncolytic vaccinia virus at a therapeutically effective dose, and the second pharmaceutical composition comprises the NK cells at a dose ranging from 1×10 7  to 1×10 10  cells/day. 
     
     
         5 . The therapeutic agent of  claim 1 , wherein the oncolytic vaccinia virus is selected from genetically mutated viruses with oncolytic abilities and wild-type viruses with oncolytic abilities. 
     
     
         6 . The therapeutic agent of  claim 1 , wherein the oncolytic vaccinia virus is functionally deficient in the TK gene and/or in the VGF gene. 
     
     
         7 . The therapeutic agent of  claim 1 , wherein the oncolytic vaccinia virus is selected from Pexa-vac, JX-963, JX-929, VSC20, GL-ONC1, and/or TG6002. 
     
     
         8 . The therapeutic agent of  claim 1 , wherein the NK cells are selected from autologous NK cells and allogeneic NK cells. 
     
     
         9 . The therapeutic agent of  claim 8 , wherein the NK cells are in vitro expanded autologous NK cells or in vitro expanded allogeneic NK cells. 
     
     
         10 . The therapeutic agent of  claim 1 , wherein the oncolytic vaccinia virus is formulated to be administered via intratumoral injection or administered intravenously; and wherein the NK cells are formulated to be administered intravenously. 
     
     
         11 . The therapeutic agent of  claim 1 , wherein the active ingredients of the first pharmaceutical composition comprise an oncolytic vaccinia virus at a dose ranging from 1×10 5  to 5×10 9  pfu/day; and wherein the active ingredients of the second pharmaceutical composition comprise the NK cells at a dose ranging from 1×10 7  to 1×10 10  cells/day. 
     
     
         12 . The therapeutic agent of  claim 1 , consisting of the first pharmaceutical composition and the second pharmaceutical composition. 
     
     
         13 . Use of the therapeutic agent of  claim 1  for preparation of drugs for treatment of tumors and/or cancers. 
     
     
         14 . The use of  claim 13 , wherein the tumors and/or cancers include lung cancer, melanoma, head and neck cancer, liver cancer, brain cancer, colorectal cancer, bladder cancer, breast cancer, ovarian cancer, uterine cancer, cervical cancer, lymph cancer, gastric cancer, esophagus cancer, renal cancer, prostate cancer, pancreatic cancer, and leukemia. 
     
     
         15 . A kit of combinational drugs with synergistic effects for treatment of tumors and/or cancers, comprising a first container containing an oncolytic vaccinia virus and a second container containing NK cells, wherein the first container is separate from the second container; and instructions specifying timing and routes of administration; wherein the oncolytic vaccinia virus can selectively replicate in tumor cells. 
     
     
         16 . The kit of  claim 15 , wherein the first container contains the oncolytic vaccinia virus at a therapeutically effective dose, and the second container contains the NK cells at a dose ranging from 1×10 7  to 1×10 10  cells/day. 
     
     
         17 . The kit of  claim 15 , wherein the oncolytic vaccinia virus is selected from genetically mutated viruses with oncolytic abilities and wild-type viruses with oncolytic abilities. 
     
     
         18 . The kit of  claim 15 , wherein the oncolytic vaccinia virus is functionally deficient in the TK gene and/or in the VGF gene. 
     
     
         19 . The kit of  claim 15 , wherein the oncolytic vaccinia virus is selected from Pexa-vac, JX-963, JX-929, VSC20, GL-ONC1, and/or TG6002. 
     
     
         20 . The kit of  claim 15 , wherein the NK cells are selected from autologous NK cells and allogeneic NK cells. 
     
     
         21 . The kit of  claim 20 , wherein the NK cells are in vitro expanded autologous NK cells or in vitro expanded allogeneic NK cells. 
     
     
         22 . The kit of  claim 15 , wherein the tumors and/or cancers include lung cancer, melanoma, head and neck cancer, liver cancer, brain cancer, colorectal cancer, bladder cancer, breast cancer, ovarian cancer, uterine cancer, cervical cancer, lymph cancer, gastric cancer, esophagus cancer, renal cancer, prostate cancer, pancreatic cancer, and leukaemia. 
     
     
         23 . The kit of  claim 15 , wherein the oncolytic vaccinia virus is formulated to be administered via intratumoral injection or administered intravenously; and wherein the NK cells are formulated to be administered intravenously. 
     
     
         24 . The kit of  claim 15 , wherein the first container contains an oncolytic vaccinia virus at a dose ranging from 1×10 5  to 5×10 9  pfu/day; and wherein the second container contains the NK cells at a dose ranging from 1×10 7  to 1×10 10  cells/day.