Vaccines for treatment and prevention of cancer

Abstract

Provided are compositions useful as therapeutic vaccines (e.g., cancer vaccines), and methods of producing such compositions. The compositions disclosed herein generally employ a stress protein and at least one synthetic peptide, which may be a phosphopeptide or phosphopeptide mimetic, comprising a cancer-specific mutation present in a patient's cancer.

1 - 147 . (canceled) 
     
     
         148 . A composition comprising at least two different complexes of a purified stress protein bound to an antigenic peptide, wherein each complex comprises a different antigenic peptide comprising:
 a) an N-terminal portion of 8-12 amino acids in length comprising at least one mutant MHC binding epitope from a cancer cell; and   b) a C-terminal portion of 11 amino acids in length comprising a heat shock protein binding sequence, wherein the amino acid sequence of the C-terminal portion consists of the amino acid sequence of SEQ ID NO: 477;   wherein at least one of the antigenic peptides in the composition comprises a modified amino acid.   
     
     
         149 . The composition of  claim 148 , wherein the modified amino acid is a Tyr, Ser, Thr, Arg, Lys, or His that has been phosphorylated on a side chain hydroxyl or amine. 
     
     
         150 . The composition of  claim 148 , wherein the modified amino acid is a mimetic of a Tyr, Ser, Thr, Arg, Lys, or His amino acid that has been phosphorylated on a side chain hydroxyl or amine. 
     
     
         151 . The composition of  claim 148 , wherein the stress protein is selected from the group consisting of hsc70, hsp70, hsp90, hsp110, grp170, gp96, calreticulin, and combinations of two or more thereof. 
     
     
         152 . The composition of  claim 151 , wherein the stress protein is hsc70. 
     
     
         153 . The composition of  claim 148 , wherein the amount of stress protein in the composition is about 10 μg-600 μg. 
     
     
         154 . The composition of  claim 153 , wherein the amount of stress protein in the composition is about 240 μg. 
     
     
         155 . The composition of  claim 148 , wherein the molar ratio of stress protein to antigenic peptide in the composition is selected from the group consisting of about 1:1, 1:2, 1:4, 1:5, 1:10, 1:20, and 1:50. 
     
     
         156 . The composition of  claim 155 , wherein the molar ratio of stress protein to antigenic peptide in the composition is about 1:1. 
     
     
         157 . The composition of  claim 148 , wherein the composition comprises at least 5 different antigenic peptides. 
     
     
         158 . The composition of  claim 148 , wherein the composition comprises at least 10 different antigenic peptides. 
     
     
         159 . The composition of  claim 148 , wherein the composition comprises at least 20 different antigenic peptides. 
     
     
         160 . The composition of  claim 148 , further comprising an adjuvant. 
     
     
         161 . The composition of  claim 160 , wherein the adjuvant comprises a saponin or an immunostimulatory nucleic acid. 
     
     
         162 . The composition of  claim 160 , wherein the adjuvant comprises QS-21. 
     
     
         163 . The composition of  claim 160 , wherein the adjuvant comprises about 1 μg-200 μg of QS-21. 
     
     
         164 . The composition of  claim 163 , wherein the adjuvant comprises about 10 μg, 25 μg, or 50 μg of QS-21. 
     
     
         165 . The composition of  claim 164 , wherein the adjuvant comprises about 50 μg of QS-21. 
     
     
         166 . The composition of  claim 165 , wherein the amount of stress protein in the composition is about 240 μg. 
     
     
         167 . The composition of  claim 166 , wherein the molar ratio of stress protein to antigenic peptide in the composition is about 1:1. 
     
     
         168 . A method of inducing a T cell response in a subject to a mutant MHC binding epitope from a cancer cell, the method comprising administering to the subject an effective amount of the composition of  claim 148 , such that a T cell response to at least one mutant MHC binding epitope in the composition is induced.