Disease therapy using dying or dead cells

Abstract

A method of treating a disease characterized by a pathological immune response in a subject in need thereof is disclosed. The method comprises administering to the subject a therapeutically effective amount of a cell preparation which comprises dying or dead leukocytes, the dying or dead leukocytes being capable of suppressing the pathological immune response, thereby treating the disease in the subject.

1 . A method of treating a disease characterized by a pathological immune response in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a cell preparation which comprises dying or dead leukocytes, said dying or dead leukocytes being capable of suppressing said pathological immune response, thereby treating the disease in the subject.  
     
     
         2 . The method of  claim 1 , wherein the method further comprises, subjecting live leukocytes to a cytocidal treatment selected from the group consisting of in-vitro serum deprivation, treatment with a steroid or steroid derivative, irradiation, and a pro-apoptotic treatment, thereby generating said dying or dead leukocytes.  
     
     
         3 . The method of  claim 1 , wherein the method further comprises inducing live leukocytes to adhere to a surface, thereby generating said dying or dead leukocytes.  
     
     
         4 . The method of  claim 1 , wherein said pathological immune response is directed against at least one antigen, and whereas said dying or dead leukocytes comprise said at least one antigen.  
     
     
         5 . The method of  claim 1 , wherein said dying or dead leukocytes are derived from the subject.  
     
     
         6 . The method of  claim 1 , wherein said dying or dead leukocytes comprise dying or dead splenocytes and/or dying or dead thymocytes.  
     
     
         7 . The method of  claim 1 , wherein said dying, or dead leukocytes comprise dying or dead lymphocytes.  
     
     
         8 . The method of  claim 11 , wherein said dying or dead leukocytes comprise dying or dead monocytes.  
     
     
         9 . The method of  claim 1 , wherein said dying or dead leukocytes comprise dying or dead neutrophils.  
     
     
         10 . The method of  claim 1 , wherein said dying or dead leukocytes comprise apoptotic leukocytes.  
     
     
         11 . The method of  claim 1 , wherein the disease is a systemic autoimmune disease.  
     
     
         12 . The method of  claim 1 , wherein the disease is an antibody-mediated autoimmune disease.  
     
     
         13 . The method of  claim 1  wherein the disease is lupus erythematosus.  
     
     
         14 . The method of  claim 1 , wherein the disease is a transplantation-related disease.  
     
     
         15 . The method of  claim 1 , wherein the disease is graft-versus-host disease.  
     
     
         16 . The method of  claim 1 , wherein said administering said cell preparation comprises administering to the subject a total number of said dying or dead leukocytes selected from a range of about 20 million to about 2 billion cells per kilogram body weight of the subject.  
     
     
         17 . The method of  claim 1 , wherein said administering said cell preparation comprises administering to the subject at least one unit dose of said dying or dead leukocytes, wherein said unit dose comprises a number of said dying or dead leukocytes selected from a range of about 4 million to about 2 billion cells per kilogram body weight of the subject.  
     
     
         18 . A device for inducing apoptosis of leukocytes, wherein the device comprises an apoptosis-inducing chamber or chambers for inducing apoptosis of leukocytes to thereby obtain apoptotic leukocytes, wherein said apoptosis-inducing chamber or chambers is selected from the group consisting of consisting of a first chamber for inducing apoptosis of monocytes, a second chamber for inducing apoptosis of neutrophils, and a third chamber for inducing apoptosis of lymphocytes.  
     
     
         19 . The device of  claim 18 , wherein said first chamber comprises a surface for enhancing adherence of monocytes thereto.  
     
     
         20 . The device of  claim 19 , wherein the device further comprises a first reservoir for containing a monocyte medium, wherein said monocyte medium is for inducing apoptosis of monocytes.  
     
     
         21 . The device of  claim 18 , wherein the device further compress a second reservoir for containing a neutrophil medium, wherein said neutrophil medium is for inducing apoptosis of neutrophils.  
     
     
         22 . The device of  claim 18 , wherein the device further comprises a third reservoir for containing a lymphocyte medium, wherein said lymphocyte medium is for inducing apoptosis of lymphocytes.  
     
     
         23 . The device: of  claim 19 , wherein the device further comprises a mechanism for resuspending surface adherent monocytes.  
     
     
         24 . The device of  claim 23 , wherein said mechanism for resuspending said surface-adherent monocytes is selected from the group consisting of: 
 a reservoir for containing a protease and a mechanism for introducing said protease into said first chamber;    a flow-generating mechanism for generating in said first chamber a flow of sufficient force and direction for resuspending said surface-adherent monocytes; and    a scraping mechanism for scraping said surface-adherent monocytes off said surface of said first chamber.    
     
     
         25 . The device of  claim 18 , wherein said apoptosis-inducing chamber or chambers comprise an apoptosis-inducing mechanism selected from the group consisting of: 
 an irradiating mechanism for inducing apoptosis;    a mechanical mechanism for inducing apoptosis; and    a chemical or biochemical substance or environment for inducing apoptosis.    
     
     
         26 . A device for treating a disease characterized by a pathological immune response, the device comprising: 
 (a) a pump for pumping blood from a subject into the device and returning blood to said subject from the device;    (b) a leukocytes separator in communication with said pump for separating circulating leukocytes from whole blood; and    (c) an apoptosis-inducing chamber or chambers in communication with said leukocytes separator for inducing apoptosis of said leukocytes to thereby obtain apoptotic leukocytes, and further in communication with said pump for administering said apoptotic leukocytes, to the subject.    
     
     
         27 . The device of  claim 26 , wherein said apoptosis inducing chambers comprise a first chamber for inducing apoptosis of monocytes, a second chamber for inducing apoptosis of neutrophils, and a third chamber for inducing apoptosis of lymphocytes.  
     
     
         28 . The device of  claim 27 , wherein said first chamber comprises a surface for enhancing adherence of monocytes thereto.  
     
     
         29 . The device of  claim 28 , wherein the device further comprises a first reservoir for containing a monocyte medium, wherein said monocyte medium is for inducing apoptosis of surface-adherent monocytes.  
     
     
         30 . The device of  claim 29 , wherein the device further comprises a second reservoir for containing a neutrophil medium, wherein said neutrophil medium is for inducing apoptosis of neutrophils.  
     
     
         31 . The device of  claim 28 , wherein the device further comprises a third reservoir for containing a lymphocyte medium, wherein said lymphocyte medium is for inducing apoptosis of lymphocytes.  
     
     
         32 . The device of  claim 28 , wherein the device further comprises a mechanism for resuspending surface-adherent monocytes.  
     
     
         33 . The device of  claim 32 , wherein said mechanism for resuspending said surface-adherent monocytes is selected from the group consisting of: 
 a reservoir for containing a protease and a mechanism for introducing said protease into said first chamber;    a flow-generating mechanism for generating in said first chamber a flow of sufficient force and direction for resuspending said surface-adherent monocytes; and    a scraping mechanism for scraping said surface-adherent monocytes off said surface of said first chamber.    
     
     
         34 . The device of  claim 26 , wherein said apoptosis-inducing chamber or chambers comprise an apoptosis-inducing mechanism selected from the group consisting of: 
 an irradiating mechanism for inducing apoptosis;    a mechanical mechanism for inducing apoptosis; and    a chemical or biochemical substance or environment for inducing apoptosis.