DNA vaccine enhancement with MHC class II activators
Methods for treating or preventing hyperproliferating diseases, e.g., cancer, are described. A method may comprise administering to a subject in need thereof a therapeutically effective amount of a nucleic acid encoding an MHC class I and/or II activator and optionally a nucleic acid encoding an antigen.
1. A composition comprising a first nucleic acid encoding the amino acid sequence of a fusion protein as set forth in SEQ ID NO: 91, wherein the fusion protein stimulates a CD4+ immune response; and a second nucleic acid encoding an antigen, wherein the first nucleic acid enhances a CD8+ T cell immune response generated from the second nucleic acid.
2. The composition of claim 1 , wherein the antigen is linked to an immunogenicity potentiating peptide (IPP).
3. The composition of claim 2 , wherein the IPP is selected from the group consisting of a cytoplasmic chaperone protein, an endoplasmic reticulum chaperone protein, a viral intercellular spreading protein, a cytoplasmic translocation polypeptide domain of a pathogenic toxin, and a polypeptide that targets the centrosome compartment of a cell, a protein involved in sorting of the lysosome-associated membrane protein type 1.
4. The composition of claim 3 , wherein the IPP is calreticulin (CRT), N-CRT, P-CRT, C-CRT, Mycobacterium tuberculosis HSP70, a protein consisting of amino acids 517-625 of M. tuberculosis HSP70, a protein consisting of amino acids 161-370 and 517-625 of M. tuberculosis HSP70, 7-tubulin, Sig/LAMP-1 or VP22.
5. A composition comprising a first nucleic acid encoding the amino acid sequence of a fusion protein as set forth in SEQ ID NO: 91, wherein the fusion protein stimulates a CD4+ immune response; a second nucleic acid encoding protein comprising the amino acid sequence as set forth in SEQ ID NO: 95, wherein the composition stimulates a CD8+ T cell immune response; and a third nucleic acid encoding an antigen, wherein the first and second nucleic acids enhance a CD8+ T cell immune response generated from the third nucleic acid.
6. The composition of claim 1 , further comprising a chemotherapeutic drug.
7. The composition of claim 6 , wherein the chemotherapeutic drug is selected from the group consisting of epigallocatechin-3-gallate (EGCG), 5,6 di-methylxanthenone-4-acetic acid (DMXAA), cisplatin, apigenin, doxorubicin, an anti-death receptor 5 antibody, a proteasome inhibitor, an inhibitor of DNA methylation, genistein, celecoxib and biologically active analogs thereof.
8. A kit comprising a first nucleic acid encoding the amino acid sequence of a fusion protein as set forth in SEQ ID NO: 91, wherein the fusion protein stimulates a CD4+ immune response; and a second a nucleic acid encoding protein comprising the amino acid sequence set forth in SEQ ID NO: 95 or a second nucleic acid encoding an antigen, wherein the first nucleic acid enhances a CD8+ T cell immune response generated from the second nucleic acid.
9. The composition of any one of claims 1 and 5 , wherein the antigen is selected from the group consisting of HPV-16 E6, HPV-16 E7, and HPV-16 E6 and E7, optionally wherein the HPV-16 E6 and/or HPV-16 E7 are detoxified.