Prostate-associated antigens and vaccine-based immunotherapy regimens

Abstract

The present disclosure provides (a) isolated immunogenic PAA polypeptides; (b) isolated nucleic acid molecules encoding immunogenic PAA polypeptides; (c) vaccine compositions comprising an immunogenic PAA polypeptide or an isolated nucleic acid molecule encoding an immunogenic PAA polypeptide; (d) methods relating to uses of the polypeptides, nucleic acid molecules, and compositions; and (e) vaccine-based immunotherapy regimens which involve co-administration of a vaccine in combination with an immune-suppressive-cell inhibitor and an immune-effector-cell enhancer.

1 - 26 . (canceled) 
     
     
         27 . A method of treating a neoplastic disorder in a mammal, comprising administering to the mammal (1) an effective amount of a vaccine capable of eliciting an immune response against a tumor-associated antigen associated with the neoplastic disorder and (2) an effective amount of an immune modulator, wherein the immune modulator is a CTLA-4 antagonist and administered locally. 
     
     
         28 . The method according to  claim 27 , wherein the CTLA-4 antagonist is administered subcutaneously. 
     
     
         29 . The method according to  claim 27 , wherein the CTLA-4 antagonist is administered intradermally. 
     
     
         30 . The method according to  claim 27 , wherein the neoplastic disorder is selected from the group consisting of prostate cancer, colorectal cancer, ovarian cancer, non-small cell lung cancer, and pancreatic cancer. 
     
     
         31 . The method according to  claim 27 , wherein the tumor-associated antigen is selected from the group consisting of PSA, PSCA, PSMA, CEA, MUC-1, TERT, 5T4, Ep-CAM, K-ras, mesothelin, EGF-R, annexin A2, and survivin. 
     
     
         32 . The method according to  claim 27 , wherein the vaccine is a nucleic acid-based vaccine. 
     
     
         33 . The method according to  claim 32 , wherein the nucleic acid-based vaccine is a viral vector-based vaccine. 
     
     
         34 . The method according to  claim 32 , wherein the nucleic acid-based vaccine is a plasmid-based vaccine. 
     
     
         35 . The method according to  claim 27 , further comprising administering to the mammal a second immune modulator. 
     
     
         36 . The method according to  claim 35 , wherein the second immune modulator is selected from the group consisting of a protein kinase inhibitor, a phosphodiesterase type 5 inhibitor, a PD-1 inhibitor, and a cyclooxygenase-2 inhibitor. 
     
     
         37 . The method according to  claim 35 , wherein the second immune modulator is a protein kinase inhibitor. 
     
     
         38 . The method according to  claim 37 , wherein the protein kinase inhibitor is axitinib or sorafenib tosylate. 
     
     
         39 . The method according to  claim 37 , wherein the protein kinase inhibitor is sunitinib. 
     
     
         40 . The method according to  claim 35 , wherein the second immune modulator is a TLR agonist. 
     
     
         41 . The method according to  claim 40 , wherein the TLR agonist is a CpG oligonucleotide. 
     
     
         42 . The method according to  claim 27 , wherein the CTLA-4 antagonist is an anti-CTLA-4 antibody. 
     
     
         43 . The method according to  claim 42 , wherein the anti-CTLA-4 antibody is ipilimumab. 
     
     
         44 . The method according to  claim 42 , wherein the anti-CTLA-4 antibody is tremelimumab. 
     
     
         45 . The method according to  claim 35 , wherein the CTLA-4 antagonist is tremelimumab and wherein the second immune modulator is sunitinib. 
     
     
         46 . The method according to  claim 35 , wherein the CTLA-4 antagonist is ipilimumab and wherein the second immune modulator is sunitinib.