Immuno-modulatory composition

Abstract

A composition for modulating the immune response in a mammal comprising a pharmaceutically acceptable carrier solution and a plurality of biodegradable nanoparticles, wherein the nanoparticles comprise a targeting moiety that is able to bind selectively to the surface of a T lymphocyte cell and/or of a vascular endothelial cell and wherein the nanoparticles further comprise leukaemia inhibitory factor (LIF). Nanoparticle-mediated targeted delivery of LIF can be used a means to guide tolerogenesis in a patient and has immediate clinical application for recipients of organ grafts and also for patients suffering from autoimmune disease.

1 . A composition for promoting an immune tolerance response in a mammal comprising:
 a) a pharmaceutically acceptable carrier solution; and   b) a plurality of biodegradable polylactidecoglycolide (PLG) polymer nanoparticles, and wherein the PLG nanoparticles further comprise:   (i) leukaemia inhibitory factor (LIF), wherein the LIF is encapsulated by the PLG nanaoparticle; and   (ii) the PLG nanoparticles comprise an outer surface, wherein a targeting moiety that is able to bind selectively to an antigen present on the surface of a T lymphocyte cell is linked to the outer surface of the PLG nanoparticles.   
     
     
         2 . The composition of  claim 1 , wherein the targeting moiety comprises a monoclonal antibody. 
     
     
         3 . The composition of  claim 1 , wherein the targeting moiety comprises a polyclonal antibody. 
     
     
         4 . The composition of  claim 1 , wherein the targeting moiety comprises an antigen-binding antibody fragment. 
     
     
         5 . The composition of  claim 4 , wherein the antigen-binding antibody fragment is selected from the group consisting of: an Fab fragment; an Fab′ fragment; an F(ab′)2 fragment; an scFv fragment. 
     
     
         6 . The composition of  claim 1 , wherein the targeting moiety binds specifically to an antigen present on the surface of the T lymphocyte cell, selected from the group consisting of: a CD4 receptor; a CD25 receptor; a gp190 receptor; a LIF receptor. 
     
     
         7 . The composition of  claim 1 , wherein the targeting moiety is an antibody that specifically binds to a CD4 receptor present on the cell surface of the T lymphocyte cell. 
     
     
         8 . A composition for promoting an immune tolerance response in a mammal comprising:
 a) a pharmaceutically acceptable carrier solution; and   b) a plurality of biodegradable polylactidecoglycolide (PLG) polymer nanoparticles, and wherein the PLG nanoparticles further comprise:   (i) leukaemia inhibitory factor (LIF), wherein the LIF is encapsulated by the PLG nanaoparticle; and   (ii) the PLG nanoparticles comprise an outer surface, wherein a targeting moiety that is able to bind selectively to an antigen present on the surface of a vascular endothelial cell is linked to the outer surface of the PLG nanoparticles.   
     
     
         9 . The composition of  claim 8 , wherein the targeting moiety comprises a monoclonal antibody. 
     
     
         10 . The composition of  claim 8 , wherein the targeting moiety comprises a polyclonal antibody. 
     
     
         11 . The composition of  claim 8 , wherein the targeting moiety comprises an antigen-binding antibody fragment. 
     
     
         12 . The composition of  claim 11 , wherein the antigen-binding antibody fragment is selected from the group consisting of: an Fab fragment; an Fab′ fragment; an F(ab′)2 fragment; an scFv fragment 
     
     
         13 . The composition of  claim 8 , wherein the targeting moiety binds specifically to an antigen present on the surface of the vascular endothelial cell, selected from the group consisting of: a CD31 receptor; a CD34 receptor; a VEGF receptor and a EPC receptor. 
     
     
         14 . The composition of  claim 1 , wherein the biodegradable polylactidecoglycolide degrades at a rate that allows for controlled release of the encapsulated LIF. 
     
     
         15 . The composition of  claim 8 , wherein the biodegradable polylactidecoglycolide degrades at a rate that allows for controlled release of the encapsulated LIF. 
     
     
         16 . A composition for promoting an immune tolerance response in a mammal comprising:
 a) a pharmaceutically acceptable carrier solution; and   b) a plurality of biodegradable polylactidecoglycolide (PLG) polymer nanoparticles, and wherein the PLG nanoparticles further comprise:   (i) leukaemia inhibitory factor (LIF), wherein the LIF is encapsulated by the PLG nanaoparticles; and   (ii) the PLG nanoparticles comprise an outer surface, and wherein a binding moiety is located on the outer surface.   
     
     
         17 . The composition of  claim 16 , wherein the binding moiety comprises avidin. 
     
     
         18 . The composition of  claim 16 , wherein the binding moiety comprises streptavidin.