Methods of treating cervical cancer

Abstract

A treatment of cervical tumor caused by human papillomavirus (HPV) infection is disclosed. Methods for improving treatment of cervical tumor caused by HPV infection are also disclosed. The methods include administering a polynucleotide encoding an E6/E7 fusion protein to a subject suffering from cervical tumor caused by HPV. The cervical tumor may be squamous cell carcinoma (SCC), adenocarcinoma, adenosquamous carcinoma, small cell carcinoma, neuroendocrine tumor (NET), glassy cell carcinoma, villoglandular adenocarcinoma (VGA), non-carcinoma malignancies, melanoma, lymphoma, or cervical intraepithelial neoplasia (CIN).

1 - 34 . (canceled) 
     
     
         35 . A method of treating a cervical tumor in a subject in need thereof, comprising
 administering to the subject a first dose of a pharmaceutical composition comprising a polynucleotide encoding a fusion protein,   administering to the subject a second dose of the composition, and   administering to the subject a third dose of the composition,   wherein the fusion protein comprises the amino acid sequences (1)-(8):   (1) an N-terminal portion of an E6 protein of HPV16,   (2) a C-terminal portion of an E6 protein of HPV16,   (3) an N-terminal portion of an E7 protein of HPV16,   (4) a C-terminal portion of an E7 protein of HPV16,   (5) an N-terminal portion of an E6 protein of HPV18,   (6) a C-terminal portion of an E6 protein of HPV18,   (7) an N-terminal portion of an E7 protein of HPV18, and   (8) a C-terminal portion of an E7 protein of HPV18,   wherein the first dose is about 1 mg to about 4 mg;   wherein the second dose is about 1 mg to about 4 mg and administered about 1 week after administering the first dose;   wherein the third dose is about 1 mg to about 4 mg and administered about 2 weeks after administering the second dose; and   wherein the method does not include a surgery for removal of the cervical tumor.   
     
     
         36 . The method of  claim 35 , wherein the method further comprises measuring a cellular immune response in the subject after the administration of the first dose, the second dose or the third dose. 
     
     
         37 . The method of  claim 35 , wherein the subject exhibits an increased cellular immune response after administration of the first dose, the second dose or the third dose. 
     
     
         38 . The method of  claim 37 , wherein said increased cellular immune response is an increase in a number of poly-functional T cells. 
     
     
         39 . The method of  claim 38 , wherein the number of the poly-functional T cells is increased at least about 5% higher than the number of the poly-functional T cells prior to the administration of the polynucleotide. 
     
     
         40 . The method of  claim 38 , wherein the increase in number of poly-functional T cells comprises an increased expression of IFN-γ, IL-2, TNF-α, MIP-β, CD107a/b, or a combination thereof or increased CD38+ Ki67+ CDS T cells. 
     
     
         41 . The method of  claim 35 , wherein the cervical tumor is squamous cell carcinoma (SCC), adenocarcinoma, adenosquamous carcinoma, small cell carcinoma, neuroendocrine tumor (NET), glassy cell carcinoma, villoglandular adenocarcinoma (VGA), non-carcinoma malignancies, melanoma, lymphoma, or cervical intraepithelial neoplasia (CIN). 
     
     
         42 . The method use of  claim 35 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 10. 
     
     
         43 . The method of  claim 35 , wherein the polynucleotide comprises the nucleotide sequence of SEQ ID NO: 9. 
     
     
         44 . The method of  claim 43 , wherein the polynucleotide further comprises a nucleic acid sequence encoding a heterologous polypeptide, wherein the heterologous polypeptide comprises an Fms-related tyrosine kinase 3 ligand (FLT3L) or a portion thereof. 
     
     
         45 . The method of  claim 44 , wherein the polynucleotide further comprises a signal peptide of tPA.