Method of making patient-specific white blood cell malignancy vaccine from membrane-proteoliposomes

Abstract

Membrane-proteoliposome structures (MPs) are useful in preparing patient-specific vaccines against specific white blood cell (WBC) malignancies. The inventive MPs typically contain a membrane component derived from a specific WBC. Other useful components include immunostimulators and exogenous lipids. The resulting vaccines are both patient- and malignancy-specific.

What is claimed is:  
     
         1 . A method of making a patient-specific vaccine for treating white blood cell malignancy, comprising combining a therapeutically effective amount of a membrane-proteoliposome (MP) with one or more pharmaceutically acceptable excipients, adjuvants, or carriers, wherein said MP contains plasma membrane from a malignant white blood cell.  
     
     
         2 . The method according to  claim 1 , wherein said malignant white blood cell is a lymphoma cell.  
     
     
         3 . The method according to  claim 1 , wherein said malignant white blood cell is a leukemia cell.  
     
     
         4 . The method according to  claim 1 , wherein said malignant white blood cell is a myeloma cell.  
     
     
         5 . A method of making a membrane-proteoliposome (MP) that comprises integral membrane from a malignant white blood cell, at least one immunostimulator, and an exogenous lipid, said method comprising: 
 (a) isolating plasma membrane from said malignant white blood cell;    (b) washing the isolated membrane of step (a) to obtain a plasma membrane suspension;    (c) subjecting the suspension of step (b) to sterilization; and    (d) entrapping an immunostimulator with the addition of an exogenous lipid, thereby providing said MP.    
     
     
         6 . The method according to  claim 5 , wherein said membrane contains at least one membrane component involved in immunity.  
     
     
         7 . The method according to  claim 6 , wherein said component is selected from the group consisting of a tumor-specific antigen, a major histocompatability complex antigen, and a costimulatory molecule.  
     
     
         8 . The method according to  claim 7 , wherein said costimulatory molecule is CD80 or CD86.  
     
     
         9 . The method according to  claim 5 , comprising at least two immunostimulators.  
     
     
         10 . The method according to  claim 5 , wherein said immunostimulator is selected from the group consisting of a lymphokine, an interferon, a cytokine, and an adjuvant.  
     
     
         11 . The method according to  claim 10 , wherein said lymphokine is IL-2.  
     
     
         12 . The method according to  claim 10 , wherein said interferon is IFN-γ.  
     
     
         13 . The method according to  claim 10 , wherein said cytokine is GM-CSF or M-CSF.  
     
     
         14 . The method according to  claim 10 , wherein said adjuvant is selected from the group consisting of monophosphoryl lipid A, lipid A, and muramyl dipeptide (MDP) lipid conjugate.  
     
     
         15 . The method according to  claim 5 , wherein said lipid is a saturated or unsaturated phospholipid or a glycolipid.  
     
     
         16 . The method according to  claim 15 , wherein said lipid is selected from the group consisting of 1,2-dimyristoylphosphatidylcholine, 1,2-dipalmitoylphosphatidylcholine, 1,2-dimyristoylphosphatidylglycerol, cholesterol, and combinations thereof.  
     
     
         17 . The method according to  claim 5 , wherein said lipid forms a membrane within which said integral membrane is patched.  
     
     
         18 . The method according to  claim 5 , wherein said lipid forms patches within said integral membrane.