Neural stem cell-mediated cancer treatment

Abstract

Provided are methods and compositions for treating cancer with a combination of neural stem cells (NSCs) and an oncolytic virus or a combination of oncolytic virotherapy and immune modulation. The method entails administrating to a subject a pharmaceutical composition comprising a combination of NSCs and an oncolytic virus, and/or NSCs packaged with one or more immunomodulatory viruses expressing one or more immunity checkpoint inhibitors, including adaptive immunity checkpoint inhibitors and innate immunity checkpoint inhibitors. The immunity checkpoint inhibitors include shRNAs against the immunity checkpoint proteins. The cancer includes but is not limited to primary, recurrent, and metastatic brain cancer, breast cancer, head and neck cancer, bladder cancer, ovarian cancer, uterine cancer, prostate cancer, skin cancer, lung cancer, and colorectal cancer.

1 . A method of treating cancer, comprising administering to a subject a pharmaceutical composition comprising neural stem cells (NSCs) packaged with one or more immunomodulatory viruses expressing one or more immunity checkpoint inhibitors. 
     
     
         2 . The method of  claim 1 , wherein the one or more immunity checkpoint inhibitors include adaptive immunity checkpoint inhibitors and innate immunity checkpoint inhibitors. 
     
     
         3 . The method of  claim 1 , wherein the immunity checkpoint inhibitors are shRNAs against immunity checkpoint proteins. 
     
     
         4 . The method of  claim 1 , wherein the cancer includes primary, recurrent, and metastatic brain cancer, breast cancer, head and neck cancer, bladder cancer, ovarian cancer, uterine cancer, prostate cancer, skin cancer, lung cancer, and colorectal cancer. 
     
     
         5 . The method of  claim 1 , wherein the cancer is peritoneal cancer selected from the group consisting of ovarian cancer, pancreatic cancer, colorectal cancer, gastric cancer, and liver cancer. 
     
     
         6 . The method of  claim 1 , wherein the cancer is metastatic ovarian cancer. 
     
     
         7 . The method of  claim 1 , wherein the NSCs are human NSCs packaged with an adenovirus expressing an adaptive immunity checkpoint inhibitor and an innate immunity checkpoint inhibitor. 
     
     
         8 . The method of  claim 7 , wherein the adenovirus is CRAd-Survivin-pk7 adenovirus. 
     
     
         9 . The method of  claim 7 , wherein (i) the adaptive immunity checkpoint inhibitor is an shRNA against PD-L1, (ii) the innate immunity checkpoint inhibitor is an shRNA against CD47, or (iii) both (i) and (ii). 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 1 , wherein the pharmaceutical composition is administered by injection. 
     
     
         12 . The method of  claim 1 , wherein the pharmaceutical composition is administered by intraperitoneal (IP) injection. 
     
     
         13 . A pharmaceutical composition for treating cancer comprising a therapeutically effective amount of neural stem cells (NSCs) packaged with one or more immunomodulatory viruses expressing one or more immune system checkpoint inhibitors. 
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the one or more immune system checkpoint inhibitors include adaptive immune system checkpoint inhibitors and innate immune system checkpoint inhibitors. 
     
     
         15 . The pharmaceutical composition of  claim 13 , wherein the immune system checkpoint inhibitors are shRNAs against immune system checkpoint proteins. 
     
     
         16 . The pharmaceutical composition of  claim 13 , wherein the cancer includes primary, recurrent, and metastatic brain cancer, breast cancer, head and neck cancer, bladder cancer, ovarian cancer, uterine cancer, prostate cancer, skin cancer, lung cancer, and colorectal cancer. 
     
     
         17 . The pharmaceutical composition of  claim 13 , wherein the cancer is peritoneal cancer selected from the group consisting of ovarian cancer, pancreatic cancer, colorectal cancer, gastric cancer, and liver cancer. 
     
     
         18 . The pharmaceutical composition of  claim 13 , wherein the cancer is metastatic ovarian cancer. 
     
     
         19 . The pharmaceutical composition of  claim 13 , wherein the NSCs are human NSCs packaged with an adenovirus expressing an adaptive immunity checkpoint inhibitor and an innate immunity checkpoint inhibitor. 
     
     
         20 . The pharmaceutical composition of  claim 19 , wherein the adenovirus is CRAd-Survivin-pk7 adenovirus. 
     
     
         21 . The pharmaceutical composition of  claim 19 , wherein (i) the adaptive immunity checkpoint inhibitor is an shRNA against PD-L1, (ii) the innate immunity checkpoint inhibitor is an shRNA against CD47, or (iii) both (i) and (ii). 
     
     
         22 - 40 . (canceled)