Immunogenic fusion proteins for the treatment of cancer
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. A recombinant Listeria monocytogenes host cell comprising a 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.
2. The recombinant Listeria monocytogenes host cell of claim 1 , wherein the Listeria monocytogenes is a ΔactA/ΔinlB mutant.
3. The recombinant Listeria monocytogenes host cell of claim 1 , 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.
4. 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 Listeria monocytogenes host cell, wherein the host cell expresses 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 the fusion proteins are encoded by a nucleic acid molecule as follows:
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.
5. The method of claim 4 , wherein the Listeria monocytogenes is a ΔactA/ΔinlB mutant.
6. The method of claim 4 , 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.
7. 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 Listeria monocytogenes host cell, wherein the host cell expresses 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.
8. The method of claim 7 , wherein the Listeria monocytogenes is a ΔactA/ΔinlB mutant.
9. The method of claim 7 , 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.