Materials and Methods for Altering an Immune Response to Exogenous and Endogenous Immunogens, Including Syngeneic and Non-Syngeneic Cells, Tissues or Organs

Abstract

Disclosed herein are materials and methods for modulating an immunologically adverse response to an exogenous or endogenous immunogen, including a cell, tissue, or organ associated immunogen. An implantable material comprising cells, such as but not limited to endothelial cells, anchored or embedded in a biocompatible matrix can modulate an adverse immune or inflammatory reaction to exogenous or endogenous immunogens, including response to non-syngeneic or syngeneic cells, tissues or organs, exogenous immunogens or stimuli, as well as ameliorate an autoimmune condition. The implantable material can be provided prior to, coincident with, or subsequent to occurrence of the immune response or inflammatory reaction. The implantable material can induce immunological acceptance in a transplant patient, reduce graft rejection and reduce donor antigen immunogenicity.

1 . A method of reducing an immune response or an inflammatory reaction, comprising the step of:
 providing to a recipient an implantable material comprising
 a biocompatible matrix; and, 
 anchored or embedded endothelial cells, endothelial-like cells, or analogs thereof, 
   wherein said implantable material is provided to said recipient in an amount sufficient to reduce the immune response or inflammatory reaction in said recipient.   
     
     
         2 . The method of  claim 1  wherein the providing step is prior to, coincident with, or subsequent to administration to said recipient of one or more doses of a cell, tissue or organ from a syngeneic or non-syngeneic donor. 
     
     
         3 . The method of  claim 1  wherein the providing step is prior to, coincident with, or subsequent to occurrence of the immune response or inflammatory reaction. 
     
     
         4 . A method of inducing acceptance in a patient, comprising the step of:
 providing an implantable material comprising a biocompatible matrix and anchored or embedded endothelial cells, endothelial-like cells, or analogs thereof, prior to, coincident with, or subsequent to transplantation of autograft, xenograft or allograft cells, tissue or organ in said patient in an amount effective to induce acceptance in said patient.   
     
     
         5 . A method of reducing donor antigen immunogenicity, comprising the step of:
 providing an implantable material comprising a biocompatible matrix and anchored or embedded endothelial cells, endothelial-like cells, or analogs thereof prior to, coincident with, or subsequent to introduction of said donor antigen to a recipient in an amount effective to reduce donor antigen immunogenicity.   
     
     
         6 . The method of  claim 1 ,  4  or  5  wherein said providing step occurs prior to, coincident with, or subsequent to administration to said recipient of an immunosuppressive agent. 
     
     
         7 . The method of  claim 6  wherein said immunosuppressive agent resides in said implantable material during coincident administration. 
     
     
         8 . The method of  claim 5  wherein said donor and recipient are the same. 
     
     
         9 . The method of  claim 1 ,  4 ,  5  or  8  wherein said recipient has an autoimmune disease. 
     
     
         10 . An implantable material suitable for use with any one of  claims 1 - 9 . 
     
     
         11 . The implantable material of  claim 10  wherein the endothelial-like cells or analogs are non-endothelial cells. 
     
     
         12 . The implantable material of  claim 10  wherein the cells are autogenic, allogenic, xenogeneic or genetically-modified variants of any one of the foregoing. 
     
     
         13 . The implantable material of  claim 10  wherein the cells are vascular endothelial cells. 
     
     
         14 . A method of transplanting to a recipient a syngeneic or non-syngeneic cell, tissue or organ transplant, comprising the step of:
 providing to said recipient an implantable material comprising a biocompatible matrix and anchored or embedded endothelial cells, endothelial-like cells, or analogs thereof, prior to, coincident with, or subsequent to transplantation such that said transplanted syngeneic or non-syngeneic cell, tissue or organ is not rejected by said recipient.   
     
     
         15 . The method of  claim 4  or  14  wherein said transplanted cell, tissue or organ comprises non-endothelial cells. 
     
     
         16 . The method of  claim 5  wherein said donor antigen comprises a non-endothelial cell antigen. 
     
     
         17 . The method of  claim 14  further comprising the step of administering an immunosuppressive agent prior to, coincident with, or subsequent to transplantation. 
     
     
         18 . A cell suitable for use with the implantable material of any one of  claims 1 - 17 . 
     
     
         19 . The cell of  claim 18  wherein said endothelial-like cell or its analog is a non-endothelial cell. 
     
     
         20 . The cell of  claim 18  wherein said analog is non-natural. 
     
     
         21 . The cell of  claim 18  wherein said cell, when anchored to or embedded within a biocompatible matrix, reduces a recipient's humoral or cellular immune response to a non-syngeneic donor cell, tissue or organ. 
     
     
         22 . The cell of  claim 18  wherein said cell, when anchored to or embedded within a biocompatible matrix, exhibits diminished immunogenicity. 
     
     
         23 . The cell of  claim 22  wherein said diminished immunogenicity is reduced expression of MHC or reduced capacity to bind, activate or promote maturation of innate immune cells, when anchored to or embedded within a biocompatible matrix, wherein said innate immune cells are selected from the group consisting of NK cells, dendritic, cells, monocytes, and macrophages. 
     
     
         24 . The cell of  claim 18  wherein said cell, when anchored to or embedded within a biocompatible matrix, exhibits reduced expression of MHC, costimulatory molecules or adhesion molecules. 
     
     
         25 . The cell of  claim 18  wherein said cell, when anchored to or embedded within a biocompatible matrix and co-cultured with a dendritic cell, inhibits expression by said dendritic cell of HLA-DR, IL12, Toll-like receptor or CD83; promotes uptake of dextran by said dendritic cell; or blocks dendritic cell-induced lymphocyte proliferation; or when co-cultured with adaptive immune cells inhibits proliferation, activation or differentiation of said cells, wherein adaptive immune cells are selected from the group consisting of B-lymphocytes and T-lymphocytes. 
     
     
         26 . An implantable material comprising a biocompatible matrix and the anchored or embedded endothelial cell, endothelial-like cell, or analog thereof of  claim 22 . 
     
     
         27 . An implantable material comprising a biocompatible matrix and the anchored or embedded endothelial cell, endothelial-like cell, or analog thereof of  claim 24 . 
     
     
         28 . An implantable material comprising a biocompatible matrix and the anchored or embedded endothelial cell, endothelial-like cell, or analog thereof of  claim 25 . 
     
     
         29 . A cell bank comprising the cell of  claim 18  or any one of  claims 23 - 25 . 
     
     
         30 . A bank of implantable material comprising the implantable material of  claim 10 . 
     
     
         31 . A bank of implantable material, wherein said implantable material comprises a biocompatible matrix and the anchored or embedded endothelial cell, endothelial-like cell, or analog thereof of  claim 22 . 
     
     
         32 . A bank of implantable material, wherein said implantable material comprises a biocompatible matrix and the anchored or embedded endothelial cell, endothelial-like cell, or analog thereof of  claim 24 . 
     
     
         33 . A bank of implantable material, wherein said implantable material comprises a biocompatible matrix and the anchored or embedded endothelial cell, endothelial-like cell, or analog thereof of  claim 25 . 
     
     
         34 . The implantable material of  claim 10  wherein said implantable material is a solid or non-solid. 
     
     
         35 . The implantable material of  claim 10  wherein said implantable material is provided to the recipient by implantation, injection or infusion. 
     
     
         36 . An implantable material for reducing an immune response to a non-syngeneic cell, tissue or organ, wherein said implantable material comprises:
 a biocompatible matrix; and, anchored thereto or embedded therein,   endothelial cells, endothelial-like cells, or analogs thereof;   or   tissue, or organ, or a segment thereof;   wherein an effective amount of said implantable material reduces the recipient's immune response to said non-syngeneic cell, tissue or organ.   
     
     
         37 . The implantable material of  claim 36  wherein said non-syngeneic cell, tissue or organ is that of the recipient suffering from an autoimmune disease. 
     
     
         38 . A method of reducing an immune response or an inflammatory reaction resulting from exposure to an exogenous immunogen, comprising the step of:
 providing to a recipient an implantable material comprising
 a biocompatible matrix; and, 
 anchored or embedded endothelial cells, endothelial-like cells, or analogs thereof, 
   wherein said implantable material is provided to said recipient in an amount sufficient to reduce the immune response or inflammatory reaction in said recipient resulting from exposure to said exogenous immunogen.   
     
     
         39 . The method of  claim 38  wherein the providing step is prior to, coincident with, or subsequent to occurrence of the immune response or inflammatory reaction. 
     
     
         40 . The method of  claim 38  wherein said exogenous immunogen is naturally occurring. 
     
     
         41 . The method of  claim 38  wherein said exogenous immunogen is selected from the group consisting of pharmaceutical agents, toxins, surgical implants, infectious agents and chemicals. 
     
     
         42 . The method of  claim 38  wherein said exogenous immunogen is an exogenous stimulus selected from the group consisting of environmental stress, injury and exposure.