Smc combination therapy for the treatment of cancer

Abstract

The present invention includes methods and compositions for enhancing the efficacy of SMCs in the treatment of cancer. In particular, the present invention includes methods and compositions for combination therapies that include an SMC and at least a second agent that stimulates one or more apoptotic or immune pathways. The second agent may be, e.g., an immunostimulatory compound or oncolytic virus.

What is claimed is: 
     
         1 . A composition comprising an SMC from Table 1 and an immunostimulatory agent from Table 2 or Table 3, wherein said SMC and said immunostimulatory agent are provided in amounts that together are sufficient to treat cancer when administered to a patient in need thereof. 
     
     
         2 . A method for treating a patient diagnosed with cancer, said method comprising administering to the patient an SMC from Table 1 and an immunostimulatory agent from Table 2 or Table 3, wherein said SMC and said immunostimulatory agent are administered simultaneously or within 28 days, 14 days, 10 days, 5 days, 24 hours, or 6 hours of each other in amounts that together are sufficient to treat said cancer. 
     
     
         3 - 8 . (canceled) 
     
     
         9 . The method of  claim 2 , wherein said SMC is a monovalent SMC. 
     
     
         10 . The method of  claim 9 , wherein said SMC is LCL161, GDC-0152/RG7419, GDC-0917/CUDC-427, or SM-406/AT-406/Debio1143. 
     
     
         11 - 12 . (canceled) 
     
     
         13 . The method of  claim 2 , wherein said SMC is a bivalent SMC. 
     
     
         14 . The method of  claim 13 , wherein said SMC is AEG40826/HGS1049, OICR720, TL32711/Birinapant, or SM-1387/APG-1387. 
     
     
         15 - 17 . (canceled) 
     
     
         18 . The method of  claim 2 , wherein said immunostimulatory agent is a TLR agonist from Table 2, a lipopolysaccharide, a peptidoglycan, a lipopeptide, a CpG oligodeoxynucleotide, or a virus from Table 3. 
     
     
         19 - 20 . (canceled) 
     
     
         21 . The method of  claim 18 , wherein said CpG oligodeoxynucleotide is CpG-ODN 2216. 
     
     
         22 . The method of  claim 18 , wherein said immunostimulatory agent is imiquimod, poly(I:C), or BCG. 
     
     
         23 - 24 . (canceled) 
     
     
         25 . The method of any one of  claim 2 , wherein said immunostimulatory agent is a virus from Table 3. 
     
     
         26 . The method of  claim 25 , wherein said virus is a vesicular stomatitis virus (VSV), adenovirus, maraba vesiculovirus, reovirus, rhabdovirus, vaccinia virus or a variant thereof, or Talimogene laherparepvec. 
     
     
         27 . The method of  claim 26 , wherein said VSV virus is VSV-M51R, VSV-MΔ51, VSV-IFNβ, or VSV-IFNβ-NIS. 
     
     
         28 - 29 . (canceled) 
     
     
         30 . The method of  claim 2 , wherein said cancer is refractory to treatment by an SMC in the absence of an immunostimulatory agent 
     
     
         31 . The method of  claim 2 , wherein said treatment further comprises administration of a therapeutic agent comprising an interferon. 
     
     
         32 . The method of  claim 31 , wherein said interferon is a type 1 interferon. 
     
     
         33 . The method of  claim 2 , wherein said cancer is selected from adrenal cancer, basal cell carcinoma, biliary tract cancer, bladder cancer, bone cancer, brain cancer, breast cancer, cervical cancer, choriocarcinoma, colon cancer, colorectal cancer, connective tissue cancer, cancer of the digestive system, endometrial cancer, epipharyngeal carcinoma, esophageal cancer, eye cancer, gallbladder cancer, gastric cancer, cancer of the head and neck, hepatocellular carcinoma, intra-epithelial neoplasm, kidney cancer, laryngeal cancer, leukemia, liver cancer, liver metastases, lung cancer, lymphoma, melanoma, myeloma, multiple myeloma, neuroblastoma, mesothelioma, neuroglioma, myelodysplastic syndrome, multiple myeloma, oral cavity cancer, ovarian cancer, paediatric cancer, pancreatic cancer, pancreatic endocrine tumors, penile cancer, plasma cell tumors, pituitary adenoma, thymoma, prostate cancer, renal cell carcinoma, cancer of the respiratory system, rhabdomyosarcoma, salivary gland cancer, sarcoma, skin cancer, small bowel cancer, stomach cancer, testicular cancer, thyroid cancer, ureteral cancer, and cancer of the urinary system. 
     
     
         34 . A composition comprising an SMC from Table 1 and an immunostimulatory agent, said immunostimulatory agent comprising:
 (a) a killed virus, an inactivated virus, or a viral vaccine; or   (b) a first agent that primes an immune response and at least a second agent that boosts said immune response,   wherein said SMC and said immunostimulatory agent are provided in amounts that together are sufficient to treat cancer when administered to a patient in need thereof.   
     
     
         35 . The composition of  claim 34 , wherein said immunostimulatory agent is an NRRP or a rabies vaccine. 
     
     
         36 . (canceled) 
     
     
         37 . The composition of  claim 36 , wherein one or both of said first agent and said second agent is an oncolytic virus vaccine, or wherein said first agent is an adenovirus carrying a tumor antigen and said second agent is a vesiculovirus. 
     
     
         38 . (canceled) 
     
     
         39 . The composition of  claim 37 , wherein said vesiculovirus is selected from Maraba-MG1 carrying the same tumor antigen as said adenovirus and Maraba-MG1 that does not carry a tumor antigen.