Pharmaceutical compositions and method for treating rheumathoid arthritis

Abstract

A method of treating rheumatoid arthritis of an individual is disclosed. The method comprises the step of expressing within the individual at least an immunologically recognizable portion of a cytokine from an exogenous polynucleotide encoding the at least a portion of the cytokine, wherein a level of expression of the at least a portion of the cytokine is sufficient to induce the formation of anti-cytokine immunoglobulins which serve for neutralizing or ameliorating the activity of a respective and/or cross reactive endogenous cytokine, to thereby treat rheumatoid arthritis.

What is claimed is:  
     
         1 . A method of treating rheumatoid arthritis of an individual, the method comprising the step of expressing within the individual at least an immunologically recognizable portion of a cytokine from an exogenous polynucleotide encoding said at least a portion of said cytokine, wherein a level of expression of said at least a portion of said cytokine is sufficient to induce a formation of anti-cytokine immunoglobulins, said anti-cytokine immunoglobulins being for neutralizing or ameliorating an activity of a respective and/or cross reactive endogenous cytokine, to thereby treat rheumatoid arthritis.  
     
     
         2 . The method of  claim 1 , wherein said cytokine is a chemokine.  
     
     
         3 . The method of  claim 2 , wherein said chemokine is a C-C chemokine.  
     
     
         4 . The method of  claim 3 , wherein said C-C chemokine is selected from the group consisting of MIP-1α, MCP-1, MIP-1β and RANTES.  
     
     
         5 . The method of  claim 1 , wherein said cytokine is TNF-α.  
     
     
         6 . The method of  claim 1 , wherein said step of expressing within the individual said at least an immunologically recognizable portion of said cytokine from said exogenous polynucleotide encoding said at least a portion of said cytokine is effected by administering said exogenous polynucleotide to the individual.  
     
     
         7 . The method of  claim 6 , wherein said exogenous polynucleotide forms a part of a pharmaceutical composition.  
     
     
         8 . The method of  claim 6 , wherein said pharmaceutical composition also includes a pharmaceutically acceptable carrier.  
     
     
         9 . The method of  claim 8 , wherein said pharmaceutically acceptable carrier is selected from the group consisting of a viral carrier, a liposome carrier, a micelle carrier and a cellular carrier.  
     
     
         10 . A method of treating rheumatoid arthritis in an individual, the method comprising the step of administering to the individual cells expressing from an exogenous polynucleotide at least an immunologically recognizable portion of a cytokine, wherein a level of expression of said at least a portion of said cytokine is sufficient to induce a formation of anti-cytokine immunoglobulins, said anti-cytokine immunoglobulins being for neutralizing or ameliorating an activity of a respective and/or cross reactive endogenous cytokine, to thereby treat rheumatoid arthritis.  
     
     
         11 . The method of  claim 10 , wherein said cells are selected from the group consisting of dendritic cells, macrophages, B cells and fibroblasts.  
     
     
         12 . The method of  claim 10 , wherein said cells are derived from the individual.  
     
     
         13 . The method of  claim 10 , wherein said cells secrete said at least a portion of said cytokine following expression thereof.  
     
     
         14 . The method of  claim 10 , wherein said cells are antigen presenting cells and as such, said cells present portions of said cytokine following expression of said at least a portion of said cytokine.  
     
     
         15 . The method of  claim 10 , wherein said cytokine is a chemokine.  
     
     
         16 . The method of  claim 15 , wherein said chemokine is a C-C chemokine.  
     
     
         17 . The method of  claim 16 , wherein said C-C chemokine is selected from the group consisting of MIP-1α, MCP-1, MIP-1β and RANTES.  
     
     
         18 . The method of  claim 10 , wherein said cytokine is TNF-α.  
     
     
         19 . The method of  claim 10 , wherein said cells expressing from said exogenous polynucleotide said at least an immunologically recognizable portion of said cytokine form a part of a pharmaceutical composition.  
     
     
         20 . A pharmaceutical composition comprising, as an active ingredient, a nucleic acid construct including a polynucleotide region encoding at least a portion of a cytokine and a pharmaceutically acceptable carrier.  
     
     
         21 . The pharmaceutical composition of  claim 20 , wherein said nucleic acid construct is a naked DNA construct.  
     
     
         22 . The pharmaceutical composition of  claim 20 , wherein said pharmaceutically acceptable carrier is selected from the group consisting of a viral carrier, a liposome carrier, a micelle carrier and a cellular carrier.  
     
     
         23 . The pharmaceutical composition of  claim 20 , wherein said polynucleotide region encoding said cytokine is under a transcriptional control of a promoter sequence.  
     
     
         24 . The pharmaceutical composition of  claim 20 , wherein said cytokine is a chemokine.  
     
     
         25 . The pharmaceutical composition of  claim 24 , wherein said chemokine is a C-C chemokine.  
     
     
         26 . The pharmaceutical composition of  claim 25 , wherein said C-C chemokine is selected from the group consisting of MIP-1α, MCP-1, MIP-1β and RANTES.  
     
     
         27 . The pharmaceutical composition of  claim 20 , wherein said cytokine is TNF-α.  
     
     
         28 . A cellular vaccine composition comprising cells expressing at least one peptide epitope derived from a cytokine, said at least one peptide includes at least 6 amino acid residues.  
     
     
         29 . The cellular vaccine composition of  claim 28 , wherein said cells are antigen presenting cells and a such said cells present said at least one peptide-epitope derived from said cytokine following expression thereof.  
     
     
         30 . The cellular vaccine composition of  claim 28 , wherein said at least one peptide-epitope derived from said cytokine is secreted from said cells following expression thereof.  
     
     
         31 . The cellular vaccine composition of  claim 28 , wherein said cytokine is a chemokine.  
     
     
         32 . The cellular vaccine composition of  claim 31 , wherein said chemokine is a C-C chemokine.  
     
     
         33 . The cellular vaccine composition of  claim 32 , wherein said C-C chemokine is selected from the group consisting of MIP-1α, MCP-1, MIP-1β and RANTES.  
     
     
         34 . The cellular vaccine composition of  claim 28 , wherein said cytokine is TNF-α.  
     
     
         35 . The cellular vaccine composition of  claim 29 , wherein said antigen presenting cells are selected from the group consisting of dendritic cells, macrophages, B cells and fibroblasts.  
     
     
         36 . A method of treating rheumatoid arthritis of an individual, the method comprising the step of expressing within the individual an exogenous polynucleotide encoding at least a portion of a variable region of an anti-cytokine immunoglobulin, wherein a level of expression of said at least a portion of said variable region of said anti-cytokine immunoglobulin is sufficient for neutralizing or ameliorating an activity of a respective and/or cross reactive endogenous cytokine, to thereby treat rheumatoid arthritis.  
     
     
         37 . The method of  claim 36 , wherein said variable region is a light chain variable region of said anti-cytokine immunoglobulin.  
     
     
         38 . The method of  claim 36 , wherein said variable region is a heavy chain variable region of said anti-cytokine immunoglobulin.  
     
     
         39 . The method of  claim 36 , wherein said cytokine is a chemokine.  
     
     
         40 . The method of  claim 39 , wherein said chemokine is a C-C chemokine.  
     
     
         41 . The method of  claim 40 , wherein said C-C chemokine is selected from the group consisting of MIP-1α, MCP-1, MIP-1β and RANTES.  
     
     
         42 . The method of  claim 36 , wherein said cytokine is TNF-α.  
     
     
         43 . A method of treating rheumatoid arthritis of an individual, the method comprising the step of administering to the individual cells expressing an exogenous polynucleotide encoding at least a portion of a variable region of an anti-cytokine immunoglobulin, wherein a level of expression of said at least a portion of said variable region of said anti-cytokine immunoglobulin is sufficient for neutralizing or ameliorating an activity of a respective and/or cross reactive endogenous cytokine, to thereby treat rheumatoid arthritis.  
     
     
         44 . The method of  claim 43 , wherein said variable region is a light chain variable region of said anti-cytokine immunoglobulin.  
     
     
         45 . The method of  claim 44 , wherein said variable region is a heavy chain variable region of said anti-cytokine immunoglobulin.  
     
     
         46 . The method of  claim 43 , wherein said cells secrete said at least a portion of said variable region of said anti-cytokine immunoglobulin following expression thereof.  
     
     
         47 . The method of  claim 43 , wherein said cytokine is a chemokine.  
     
     
         48 . The method of  claim 47 , wherein said chemokine is a C-C chemokine.  
     
     
         49 . The method of  claim 48 , wherein said C-C chemokine is selected from the group consisting of MIP-1α, MCP-1, MIP-1β and RANTES.  
     
     
         50 . The method of  claim 43 , wherein said cytokine is TNF-α.  
     
     
         51 . A pharmaceutical composition comprising, as an active ingredient, a nucleic acid construct including a polynucleotide region encoding at least a portion of a variable region of an anti-cytokine immunoglobulin and a pharmaceutically acceptable carrier, wherein said at least a portion of said variable region is capable of binding said cytokine.  
     
     
         52 . The pharmaceutical composition of  claim 51 , wherein said variable region is a light chain variable region of said anti-cytokine immunoglobulin.  
     
     
         53 . The pharmaceutical composition of  claim 51 , wherein said variable region is a heavy chain variable region of said anti-cytokine immunoglobulin.  
     
     
         54 . The pharmaceutical composition of  claim 51 , wherein said cytokine is a chemokine.  
     
     
         55 . The pharmaceutical composition of  claim 54 , wherein said chemokine is a C-C chemokine.  
     
     
         56 . The pharmaceutical composition of  claim 55 , wherein said C-C chemokine is selected from the group consisting of MIP-1α, MCP-1, MIP-1β and RANTES.  
     
     
         57 . The pharmaceutical composition of  claim 51 , wherein said cytokine is TNF-α.  
     
     
         58 . A cellular vaccine composition comprising cells expressing at least a portion of a variable region of an anti-cytokine immunoglobulin, wherein said portion of said variable region of said anti-cytokine immunoglobulin is capable of binding said cytokine.  
     
     
         59 . The cellular vaccine composition of  claim 58 , wherein said variable region is a light chain variable region of said anti-cytokine immunoglobulin.  
     
     
         60 . The cellular vaccine composition of  claim 58 , wherein said variable region is a heavy chain variable region of said anti-cytokine immunoglobulin.  
     
     
         61 . The cellular vaccine composition of  claim 58 , wherein said cells secrete said at least a portion of said variable region of said anti-cytokine immunoglobulin following expression thereof.  
     
     
         62 . The cellular vaccine composition of  claim 58 , wherein said cytokine is a chemokine.  
     
     
         63 . The cellular vaccine composition of  claim 62 , wherein said chemokine is a C-C chemokine.  
     
     
         64 . The cellular vaccine composition of  claim 63 , wherein said C-C chemokine is selected from the group consisting of MIP-1α, MCP-1, MIP-1β and RANTES.  
     
     
         65 . The cellular vaccine composition of  claim 58 , wherein said cytokine is TNF-α.