Anticancer composition comprising tumor-specific oncolytic adenovirus and immune checkpoint inhibitor

Abstract

The present invention relates to an anticancer composition comprising a tumor-specific oncolytic adenovirus and an immune checkpoint inhibitor. The recombinant adenovirus having IL-12 and shVEGF, or IL-12 and GM-CSF-RLX inserted therein, according to the present invention, exhibits an excellent anticancer effect by enhancing immune functions, and such anticancer effect has been confirmed to be notably enhanced through concomitant administration with an immune checkpoint inhibitor, and thus the present invention may be used as a key technique in the field of cancer treatment.

What is claimed is: 
     
         1 . A recombinant oncolytic adenovirus comprising: a gene encoding Interleukin 12 (IL-12); and a gene encoding a shRNA suppressing the expression of VEGF (Vascular endothelial growth factor). 
     
     
         2 . The recombinant oncolytic adenovirus of  claim 1 , wherein the recombinant adenovirus has any one or more regions selected from the group consisting of E1B and E3 regions deleted. 
     
     
         3 . The recombinant oncolytic adenovirus of  claim 2 , wherein in the recombinant adenovirus the gene encoding IL-12 is inserted into the E1B region, and
 the gene encoding a shRNA suppressing the expression of VEGF (Vascular endothelial growth factor) is inserted into the E3 region.   
     
     
         4 . A pharmaceutical composition for preventing or treating cancer, the composition comprising: (a) the recombinant oncolytic adenovirus of  claim 1 ; and (b) a pharmaceutically acceptable carrier. 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein the composition further comprises immune checkpoint inhibitors. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the immune checkpoint inhibitor is any one selected from the group consisting of a programmed cell death-1 (PD-1) antagonist, a programmed cell death-ligand 1 (PD-L1) antagonist, a programmed cell death-ligand 2 (PD-L2) antagonist, a cluster of differentiation 27 (CD27) antagonist, a cluster of differentiation 28 (CD28) antagonist, a cluster of differentiation 70 (CD70) antagonist, a cluster of differentiation 80 (CD80, also known as B7-1) antagonist, a cluster of differentiation 86 (CD86, also known as B7-2) antagonist, a cluster of differentiation 137 (CD137) antagonist, a cluster of differentiation 276 (CD276) antagonist, a killer-cell immunoglobulin-like receptors (KIRs) antagonist, a lymphocyte-activation gene 3 (LAG3) antagonist, a tumor necrosis factor receptor superfamily, member 4 (TNFRSF4, also known as CD134) antagonist, a glucocorticoid-induced TNFR-related protein (GITR) antagonist, a glucocorticoid-induced TNFR-related protein ligand (GITRL) antagonist, a 4-1BB ligand (4-1BBL) antagonist, a cytolytic T lymphocyte associated antigen-4 (CTLA-4) antagonist, an adenosine A2A receptor (A2AR) antagonist, a V-set domain-containing T-cell activation inhibitor 1 (VTCN1) antagonist, a B- and T-lymphocyte attenuator (BTLA) antagonist, an indoleamine 2,3-dioxygenase (IDO) antagonist, a T-cell Immunoglobulin domain and Mucin domain 3 (TIM-3) antagonist, a V-domain Ig suppressor of T cell activation (VISTA) antagonist, a killer cell lectin-like receptor subfamily A (KLRA) antagonist, and a combination thereof. 
     
     
         7 . The pharmaceutical composition of  claim 4 , wherein the cancer is any one selected from the group consisting of gastric cancer, lung cancer, non-small cell lung cancer, breast cancer, ovarian cancer, liver cancer, bronchial cancer, nasopharyngeal cancer, laryngeal cancer, pancreatic cancer, bladder cancer, colon cancer, cervical cancer, bone cancer, non-small cell bone cancer, hematologic malignancy, skin cancer, head and neck cancer, uterine cancer, colorectal cancer, anal near cancer, fallopian tube cancer, endometrial cancer, vaginal cancer, vulva cancer, Hodgkin's disease, esophageal cancer, small intestine cancer, endocrine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, chronic or acute leukemia, lymphocytic lymphoma, kidney or hydroureter cancer, renal cell carcinoma, renal pelvic carcinoma, salivary gland cancer, sarcoma cancer, pseudomyxoma peritonei, hepatoblastoma, testicular cancer, glioblastoma, cheilocarcinoma, ovarian germ cell tumors, basal cell carcinoma, multiple myeloma, gallbladder cancer, choroidal melanoma, cancer of the ampulla of Vater, peritoneal cancer, tongue cancer, small cell cancer, pediatric lymphoma, neuroblastoma, duodenal cancer, astrocytoma, meningioma, renal pelvis cancer, pudendum cancer, thymus cancer, central nervous system (CNS) tumors, primary central nervous system lymphoma, spinal cord tumors, brain stem neuroglioma, and pituitary adenoma. 
     
     
         8 . The pharmaceutical composition of  claim 4 , wherein the cancer is a recurrent cancer. 
     
     
         9 . The pharmaceutical composition of  claim 4 , wherein the composition enhances anti-tumor immunity. 
     
     
         10 . A method for treating cancer comprising administering a composition comprising the recombinant oncolytic adenovirus of  claim 1 ; and a pharmaceutically acceptable carrier, to an individual. 
     
     
         11 . The method according to  claim 10 ,
 wherein the composition is administrated simultaneously, separately, or sequentially in combination with an immune checkpoint inhibitor.