Using heat shock proteins to improve the therapeutic benefit of a non-vaccine treatment modality

Abstract

The present invention relates to methods of improving a treatment outcome comprising administering a heat shock protein (HSP) preparation or an α-2-macroglobulin (α2M) preparation with a non-vaccine treatment modality. In particular, an HSP preparation or an α2M preparation is administered in conjunction with a non-vaccine treatment modality for the treatment of cancer or infectious diseases. In the practice of the invention, a preparation comprising HSPs such as but not limited to, hsp70, hsp90 and gp96 alone or in combination with each other, noncovalently or covalently bound to antigenic molecules or α2M, noncovalently or covalently bound to antigenic molecules is administered in conjunction with a non-vaccine treatment modality.

1 - 33 . (canceled) 
     
     
         34 . A method of treating cancer in a subject in need thereof, the method comprising:
 administering to the subject a monoclonal antibody and a purified heat shock protein preparation comprising a heat shock protein-peptide complex comprising a heat shock protein covalently or noncovalently attached to an antigenic peptide, wherein the antigenic peptide displays antigenicity of an antigen of the cancer, wherein the combination of the monoclonal antibody and the purified heat shock protein preparation produces a synergistic therapeutic effect for treating the cancer.   
     
     
         35 . The method of  claim 34 , wherein the treatment results in an increase in the number of natural killer (NK) cells, mature dendritic cells, CD4+ T cells and/or CD8+ T cells in the subject. 
     
     
         36 . The method of  claim 34 , wherein the cancer is a glioma. 
     
     
         37 . The method of  claim 34 , wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes that comprise one or more of hsp70, hsp90, hsp110, gp96, grp170, and calreticulin. 
     
     
         38 . The method of  claim 34 , wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes that comprise gp96. 
     
     
         39 . The method of  claim 34 , comprising administering the purified heat shock protein preparation once a week for the first 4 weeks. 
     
     
         40 . The method of  claim 39 , comprising administering the purified heat shock protein once every other week after the first 4 weeks of administration. 
     
     
         41 . The method of  claim 34 , wherein the purified heat shock protein preparation and the monoclonal antibody are administered 2 to 4 days apart, 4 to 6 days apart, 1 week apart, 1 to 2 weeks apart, or 2 to 4 weeks apart. 
     
     
         42 . The method of  claim 34 , comprising administering the purified heat shock protein preparation for a first period of time, followed by administering the monoclonal antibody for a second period of time, and repeating this sequential administration. 
     
     
         43 . The method of  claim 34 , wherein the monoclonal antibody is administered prior to the initial administration of the purified heat shock protein preparation. 
     
     
         44 . The method of  claim 34 , wherein the monoclonal antibody is administered concurrently with the administration of the purified heat shock protein preparation. 
     
     
         45 . The method of  claim 34 , wherein the monoclonal antibody is administered subsequent to the initial administration of the purified heat shock protein preparation. 
     
     
         46 . The method of  claim 34 , wherein the monoclonal antibody and the purified heat shock protein preparation are cyclically administered. 
     
     
         47 . The method of  claim 34 , wherein the purified heat shock protein preparation is autologous to the subject. 
     
     
         48 . The method of  claim 34 , wherein the subject is human. 
     
     
         49 . The method of  claim 48 , wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes isolated from cells of the cancer of the subject. 
     
     
         50 . The method of  claim 34 , wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes comprising heat shock proteins non-covalently attached to antigenic peptides. 
     
     
         51 . The method of  claim 34 , wherein the purified heat shock protein preparation comprises heat shock protein-peptide complexes isolated from cells of the cancer. 
     
     
         52 . The method of  claim 34 , wherein the antigenic peptide displays antigenicity of a tumor-specific antigen or a tumor-associated antigen of the cancer in the subject.