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 . A method of treating cancer in a subject comprising: 
 (a) administering to the subject at least one treatment modality, wherein said at least one treatment modality comprises a tyrosine kinase inhibitor; and    (b) administering a purified heat shock protein preparation.    
   
   
       2 . The method of  claim 1  wherein the cancer is chronic myelogenous leukemia.  
   
   
       3 . The method of  claim 2  wherein the cancer is in chronic phase.  
   
   
       4 . The method of  claim 1  wherein the cancer is a soft tissue sarcoma.  
   
   
       5 . The method of  claim 1  wherein the cancer is a gastrointestinal stromal tumor expressing the tyrosine kinase receptor c-kit.  
   
   
       6 . The method of  claim 1  wherein the tyrosine kinase inhibitor is a tyrphostin.  
   
   
       7 . The method of  claim 1  wherein the tyrosine kinase inhibitor is selected from the group consisting of imatinib mesylate, herbimycin A, genistein, erbstatin, and lavendustin A.  
   
   
       8 . The method of  claim 1  wherein the tyrosine kinase inhibitor is imatinib mesylate.  
   
   
       9 . The method of  claim 8  wherein the imatinib mesylate is purified.  
   
   
       10 . The method of  claim 1  wherein the subject has previously been non-responsive to treatment with at least one treatment modality in the absence of a heat shock protein preparation.  
   
   
       11 . The method of  claim 1  wherein the purified heat shock protein preparation comprises one or more heat shock protein-peptide complexes wherein the heat shock protein is hsp60, hsp70, hsp90, hsp110, gp96, or calreticulin.  
   
   
       12 . The method of  claim 1  wherein the purified heat shock protein preparation comprises hsp70.  
   
   
       13 . The method of  claim 1  wherein the purified heat shock protein is autologous to the subject being treated.  
   
   
       14 . The method of  claim 1  wherein the subject is human.  
   
   
       15 . The method of  claim 1  wherein the treatment modality is administered prior to the initial administration of the heat shock protein preparation.  
   
   
       16 . The method of  claim 1  wherein the treatment modality is administered concurrently with the administration of the heat shock protein preparation.  
   
   
       17 . The method of  claim 1  wherein the treatment modality is administered subsequent to the initial administration of the heat shock protein preparation.  
   
   
       18 . A method of treating chronic myelogenous leukemia in a subject comprising: 
 (a) administering to the subject at least one treatment modality, wherein said at least one treatment modality comprises imatinib mesylate; and    (b) administering a purified heat shock protein preparation.    
   
   
       19 . The method of  claim 18  wherein the subject is human.  
   
   
       20 . The method of  claim 18  wherein said imatinib mesylate is administered daily.  
   
   
       21 . The method of  claim 20  wherein said imatinib mesylate is administered at 400 mg daily.  
   
   
       22 . The method of  claim 20  wherein said imatinib mesylate is administered at 600 mg daily.  
   
   
       23 . The method of  claim 20  wherein said imatinib mesylate is administered at 800 mg in two daily doses of 400 mg each.  
   
   
       24 . The method of  claim 18  wherein said imatinib mesylate is administered prior to initial administration to the subject of the heat shock protein preparation.  
   
   
       25 . The method of  claim 18  wherein said imatinib mesylate is administered concurrently with said administering of the heat shock protein preparation.  
   
   
       26 . The method of  claim 18  wherein said imatinib mesylate is administered subsequent to initial administration to the subject of the heat shock protein preparation.  
   
   
       27 . A method of treating CML in a subject receiving 200 mg to 800 mg of imatinib mesylate daily comprising administering a heat shock protein preparation to said subject, wherein said heat shock protein preparation comprises hsp70-peptide complexes.  
   
   
       28 . The method of  claim 27  wherein said hsp70-peptide complexes are isolated from tumor cells obtained from said subject.  
   
   
       29 . The method of  claim 27  wherein said heat shock protein preparation is administered once a week.  
   
   
       30 . A kit comprising a first container containing a purified heat shock protein preparation and a second container containing imatinib mesylate.  
   
   
       31 . The kit of  claim 30  wherein said heat shock protein preparation comprises hsp70-peptide complexes.  
   
   
       32 . A pharmaceutical composition comprising a purified heat shock protein preparation and imatinib mesylate.  
   
   
       33 . The pharmaceutical composition of  claim 32  wherein said heat shock protein preparation comprises hsp-peptide complexes.