Immunogenic Fusion Proteins For The Treatment Of Cancer

Abstract

Provided herein are compositions and methods for eliciting an immune response in a subject. In particular, the present disclosure is directed to immunogenic fusion proteins and methods of eliciting an immune response using host cells comprising nucleic acid molecules encoding said fusion proteins.

1 .- 195 . (canceled) 
     
     
         196 . A recombinant nucleic acid molecule encoding three separate fusion proteins, wherein the three separate fusion proteins are EGFRvIIIx5-SSX2, EGFRvIIIx5-PAP 33-386 , and EGFRvIIIx5-NKX3.1(R41G) 11-234 -PSMA 1-20, 44-138, 169-750 , and wherein:
 a) EGFRvIIIx5-SSX2 is encoded by a nucleic acid sequence comprising the sequence set forth in SEQ ID NO:3;   b) EGFRvIIIx5-PAP 33-386  is encoded by a nucleic acid sequence comprising the sequence set forth in SEQ ID NO:11; and   c) EGFRvIIIx5-NKX3.1(R41G) 11-234 -PSMA 1-20, 44-138, 169-750  is encoded by a nucleic acid sequence comprising the sequence set forth in SEQ ID NO:15.   
     
     
         197 . The nucleic acid molecule of  claim 196 , further comprising a promoter, a signal sequence, or both, wherein the promoter, signal sequence, or both are operably linked with the nucleotide sequence encoding the EGFRvIIIx5 polypeptide and the nucleotide sequence encoding the SSX2 polypeptide. 
     
     
         198 . The nucleic acid molecule of  claim 196  which is operably linked to an ActA promoter, said ActA promoter having the sequence set forth in SEQ ID NO:21. 
     
     
         199 . A method of eliciting an immune response in a subject, said method comprising administering to the subject a therapeutically effective amount of a composition comprising a recombinant nucleic acid molecule, wherein the nucleic acid molecule encodes the fusion proteins EGFRvIIIx5-SSX2, EGFRvIIIx5-PAP 33-386 , and EGFRvIIIx5-NKX3.1(R41G) 11-234 -PSMA 1-20, 44-138, 169-750 , and wherein:
 a) EGFRvIIIx5-SSX2 is encoded by a nucleic acid sequence comprising the sequence set forth in SEQ ID NO:3;   b) EGFRvIIIx5-PAP 33-386  is encoded by a nucleic acid sequence comprising the sequence set forth in SEQ ID NO:11; and   c) EGFRvIIIx5-NKX3.1(R41G) 11-234 -PSMA 1-20, 44-138, 169-750  is encoded by a nucleic acid sequence comprising the sequence set forth in SEQ ID NO:15.   
     
     
         200 . The method of  claim 199 , wherein the nucleic acid molecule further comprises a promoter, a signal sequence, or both, and wherein the promoter, signal sequence, or both are operably linked with the nucleotide sequence encoding the EGFRvIIIx5 polypeptide and the nucleotide sequence encoding the SSX2 polypeptide. 
     
     
         201 . The method of  claim 199 , wherein the nucleic acid molecule is operably linked to an ActA promoter, said ActA promoter having the sequence set forth in SEQ ID NO:21. 
     
     
         202 . A method of treating cancer in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a composition comprising a nucleic acid molecule which encodes the fusion EGFRvIIIx5-SSX2, EGFRvIIIx5-PAP 33-386 , and EGFRvIIIx5-NKX3.1(R41G) 11-234 -PSMA 1-20, 44-138, 169-750 , and wherein:
 a) EGFRvIIIx5-SSX2 is encoded by a nucleic acid sequence comprising the sequence set forth in SEQ ID NO:3;   b) EGFRvIIIx5-PAP 33-386  is encoded by a nucleic acid sequence comprising the sequence set forth in SEQ ID NO:11; and   c) EGFRvIIIx5-NKX3.1(R41G) 11-234 -PSMA 1-20, 44-138, 169-750  is encoded by a nucleic acid sequence comprising the sequence set forth in SEQ ID NO:15.   
     
     
         203 . The method of  claim 202 , wherein the nucleic acid molecule further comprises a promoter, a signal sequence, or both, and wherein the promoter, signal sequence, or both are operably linked with the nucleotide sequence encoding the EGFRvIIIx5 polypeptide and the nucleotide sequence encoding the SSX2 polypeptide. 
     
     
         204 . The method of  claim 202 , wherein the nucleic acid molecule is operably linked to an ActA promoter, said ActA promoter having the sequence set forth in SEQ ID NO:21. 
     
     
         205 . The nucleic acid molecule of  claim 196 , said nucleic acid molecule being part of an expression cassette. 
     
     
         206 . A vector comprising the nucleic acid molecule of  claim 196 . 
     
     
         207 . The nucleic acid molecule of  claim 198 , said nucleic acid molecule being part of an expression cassette. 
     
     
         208 . A vector comprising the nucleic acid molecule of  claim 198 .