Purification of heat shock/stress protein cell surface receptors and their use as immunotherapeutic agents

Abstract

The present invention relates to receptors for heat shock proteins (HSPs), such as gp96, Hsp70 and Hsp90. The receptor is associated with the cell membranes of a subset of antigen presenting cells, such as macrophages, dendritic cells. The invention provides methods for identifying and isolating cells that express the heat shock protein receptor, the heat shock protein receptor, antibodies to heat shock protein receptor and nucleic acid molecules encoding heat shock protein receptor, and fragments thereof. The present invention further provides methods of use of the heat shock protein receptor positive cells, heat shock protein receptor protein, heat shock protein receptor antibodies, and heat shock protein receptor gene. Methods for identifying a molecule that enhance or block the function of heat shock protein receptor are included in the invention. The compositions of the invention may be used in various diagnostic and therapeutic applications in the area of cancer and infectious diseases.

1 - 12  (canceled)  
     
     
         13  A method for isolating a heat shock protein receptor comprising: 
 (a) preparing an extract of heat shock protein receptor positive cells;    (b) contacting a heat shock protein with the extract for a time period and under conditions sufficient for the heat shock protein receptor in the extract to bind the heat shock protein; and    (c) recovering the heat shock protein receptor bound to the heat shock protein.    
     
     
         14  The method of  claim 13  wherein the heat shock protein comprises an affinity tag and wherein the method further comprises contacting the extract and the heat shock protein with a solid phase containing a binding partner of the affinity tag for a time period and under conditions sufficient to allow binding of the heat shock protein to the solid phase prior to step (c).  
     
     
         15  A method for isolating a heat shock protein receptor comprising: 
 (a) preparing an extract of heat shock protein receptor positive cells;    (b) contacting an antibody to heat shock protein receptor with the extract for a time period and under conditions sufficient for the heat shock protein receptor in the extract to bind to the antibody; and    (c) recovering the bound heat shock protein receptor from the antibody.    
     
     
         16  The method of  claim 15  wherein the antibody comprises an affinity tag and wherein the method further comprises prior to step (c) the step of contacting the antibody bound to heat shock protein receptor from the extract bound to heat shock protein receptor from the extract with a solid phase containing a binding partner of the affinity tag for a time period and under conditions sufficient to allow binding of the affinity tag to the binding partner on the solid phase prior to step (c).  
     
     
         17  A purified heat shock protein receptor which is isolated according to the method of  claim 14 ,  15 , or  16 .  
     
     
         18  The heat shock protein receptor of  claim 17  is a gp96 receptor.  
     
     
         19  The heat shock protein receptor of  claim 17  selected from the group consisting of an Hsp70 receptor, an Hsp 90 receptor, an Hsp100 receptor, and an smHsp receptor.  
     
     
         20  The heat shock protein receptor of  claim 17  which is a human heat shock protein receptor.  
     
     
         21 - 52  (canceled)