Polynucleotides for treating oncogenic viral polypeptide positive tumors

Abstract

This document relates to polynucleotides encoding antigenic polypeptides to induce an immune response to oncogenic viral polypeptides. Also provided are compositions comprising polynucleotides encoding antigenic polypeptides, and methods of use. In the provided methods, the virus can be a human papilloma virus. In some embodiments, a method for killing a cell expressing a first oncogenic viral polypeptide in a subject is provided. The method includes administering to the subject a composition in an amount sufficient to initiate an immune response against the first oncogenic viral peptide, where the composition comprises a pharmaceutically acceptable carrier and a polynucleotide provided herein and the immune response is effective to cause a cytotoxic effect in the cell. In some embodiments, the polynucleotide includes a second nucleotide sequence encoding a second antigenic polypeptide. The first oncogenic viral polypeptide can be E6 and the second oncogenic viral polypeptide can be E7.

1 . An isolated polynucleotide comprising a first nucleotide sequence encoding a first antigenic polypeptide, wherein the first antigenic polypeptide:
 a. comprises an amino acid sequence having at least 70% sequence identity to the amino acid sequence of a first oncogenic viral polypeptide;   b. is capable of initiating an immune response to the first oncogenic viral polypeptide in an immune-competent host; and   c. is non-oncogenic in the immune-competent host.   
     
     
         2 . The polynucleotide of  claim 1 , wherein the polynucleotide comprises a second nucleotide sequence encoding a second antigenic polypeptide, wherein the second antigenic polypeptide:
 a. comprises an amino acid sequence having at least 70% sequence identity to the amino acid sequence of a second oncogenic viral polypeptide;   b. is capable of initiating an immune response to the second oncogenic viral polypeptide in the immune-competent host; and   c. is non-oncogenic in the immune-competent host.   
     
     
         3 . The polynucleotide of  claim 2 , wherein the virus is a human papilloma virus. 
     
     
         4 . The polynucleotide of  claim 3 , wherein the first oncogenic viral polypeptide is E6 and the second oncogenic viral polypeptide is E7. 
     
     
         5 . The polynucleotide of  claim 4 , wherein the first nucleotide sequence encodes SEQ ID NO:2 having a mutation selected from the group consisting of:
 a. a point mutation or deletion at L50;   b. a point mutation or deletion at E148;   c. a point mutation or deletion at T149;   d. a point mutation or deletion at Q150; and   e. a point mutation or deletion at L151.   
     
     
         6 . The polynucleotide of  claim 4 , wherein the second nucleotide sequence encodes SEQ ID NO:4 having a mutation selected from the group consisting of:
 a. a point mutation or deletion at H2;   b. a point mutation or deletion at C24;   c. a point mutation or deletion at E46; and   d. a point mutation or deletion at L67.   
     
     
         7 . The polynucleotide of  claim 4 , wherein the first nucleotide sequence encodes SEQ ID NO:29 and the second nucleotide sequence encodes SEQ ID NO:30. 
     
     
         8 . A composition comprising:
 a. a pharmaceutically acceptable carrier; and   b. a polynucleotide, said polynucleotide comprising a first nucleotide sequence encoding a first antigenic polypeptide, wherein the first antigenic polypeptide:
 i. comprises an amino acid sequence having at least 70% sequence identity to the amino acid sequence of a first oncogenic viral polypeptide; 
 ii. is capable of initiating an immune response to the first oncogenic viral polypeptide in an immune-competent host; and 
 iii. is non-oncogenic in the immune-competent host. 
   
     
     
         9 . The composition of  claim 8 , wherein the polynucleotide comprises a second nucleotide sequence encoding a second antigenic polypeptide, wherein the second antigenic polypeptide:
 a. comprises an amino acid sequence having at least 70% sequence identity to the amino acid sequence of a second oncogenic viral polypeptide;   b. is capable of initiating an immune response to the second oncogenic viral polypeptide in the immune-competent host; and   c. is non-oncogenic in the immune-competent host.   
     
     
         10 . The composition of  claim 9 , wherein the virus is a human papilloma virus. 
     
     
         11 . The composition of  claim 10 , wherein the first oncogenic viral polypeptide is E6 and the second oncogenic viral polypeptide is E7. 
     
     
         12 . The composition of  claim 11 , wherein the first nucleotide sequence encodes SEQ ID NO:2 having a mutation selected from the group consisting of:
 a. a point mutation or deletion at L50;   b. a point mutation or deletion at E148;   c. a point mutation or deletion at T149;   d. a point mutation or deletion at Q150; and   e. a point mutation or deletion at L151.   
     
     
         13 . The composition of  claim 11 , wherein the second nucleotide sequence encodes SEQ ID NO:4 having a mutation selected from the group consisting of:
 a. a point mutation or deletion at H2;   b. a point mutation or deletion at C24;   c. a point mutation or deletion at E46; and   d. a point mutation or deletion at L67.   
     
     
         14 . The composition of  claim 11 , wherein the first nucleotide sequence encodes SEQ ID NO:29 and the second nucleotide sequence encodes SEQ ID NO:30. 
     
     
         15 . The composition of  claim 8 , wherein the pharmaceutically acceptable carrier is an adenovirus envelope. 
     
     
         16 . A method for killing a cell expressing a first oncogenic viral polypeptide in a subject, the method comprising administering to the subject a composition in an amount sufficient to initiate an immune response against said first oncogenic viral peptide, the composition comprising:
 a. a pharmaceutically acceptable carrier; and   b. a polynucleotide, said polynucleotide comprising a first nucleotide sequence encoding a first antigenic polypeptide, wherein the first antigenic polypeptide:
 i. comprises an amino acid sequence having at least 70% sequence identity to the amino acid sequence of a first oncogenic viral polypeptide; 
 ii. is capable of initiating an immune response to the first oncogenic viral polypeptide in an immune-competent host; and 
 iii. is non-oncogenic in the immune-competent host; 
   
       said immune response effective to cause a cytotoxic effect in said cell. 
     
     
         17 . The method of  claim 16 , wherein the polynucleotide comprises a second nucleotide sequence encoding a second antigenic polypeptide, wherein the second antigenic polypeptide:
 a. comprises an amino acid sequence having at least 70% sequence identity to the amino acid sequence of a second oncogenic viral polypeptide;   b. is capable of initiating an immune response to the second oncogenic viral polypeptide in the immune-competent host; and   c. is non-oncogenic in the immune-competent host.   
     
     
         18 . The method of  claim 17 , wherein said cell is part of a neoplasia. 
     
     
         19 . The method of  claim 18 , wherein said neoplasia is malignant. 
     
     
         20 . The method of  claim 17 , wherein the virus is a human papilloma virus. 
     
     
         21 .- 25 . (canceled)