Reducer of immunosuppression by tumor cell and antitumor agent using the same

Abstract

In order to provide a gene expression enhancer for enhancing expression of FoxP3 gene in a cell; a cell differentiation inducer for inducing differentiation of a cell into a regulatory T cell; an immunosuppressor for suppressing immunity and an agent for treating hyperimmune diseases based on the abovementioned actions; an inhibitor of enhancement of gene expression for inhibiting enhancement of expression of FoxP3 gene in a cell; an inhibitor of induction of cell differentiation for inhibiting induction of differentiation of a cell into a regulatory T cell; a reducer of immunosuppression for reducing immunosuppression, a stimulator of tumor immunity and an antitumor agent based on the abovementioned actions; and the like, for example, an agent containing at least one of a cell expressing Snail protein, MCP1 protein, FSTL1 protein, membrane IL-13Ra2 protein or secretory IL-13Ra2 protein, or MCP1 protein, FSTL1 protein or secretory IL-13Ra2 protein, is used as a gene expression enhancer for FoxP3, an inducer of regulatory T cell differentiation, an immunosuppressor or an agent for treating hyperimmune diseases; and an agent containing an anti-MCP1 antibody, an anti-FSTL1 antibody or an anti-IL-13Ra2 antibody is used as an inhibitor of enhancement of FoxP3 gene expression, a reducer of immunosuppression, a stimulator of tumor immunity, an antitumor agent, or the like.

1 . A gene expression enhancer for enhancing expression of FoxP3 gene in a cell, wherein the enhancer activates MCP1 signaling in the cell. 
     
     
         2 . A gene expression enhancer for enhancing expression of FoxP3 gene in a cell, comprising a cell expressing a Snail protein, an MCP1 protein, an FSTL1 protein, a membrane IL-13Ra2 protein or a secretory IL-13Ra2 protein. 
     
     
         3 . A gene expression enhancer for enhancing expression of FoxP3 gene in a cell, comprising an MCP1 protein, an FSTL1 protein or a secretory IL-13Ra2 protein. 
     
     
         4 . The gene expression enhancer according to  claim 3 , comprising a culture supernatant of a cell expressing a Snail protein or a cell secreting an MCP1 protein, an FSTL1 protein or a secretory IL-13Ra2 protein. 
     
     
         5 . The gene expression enhancer according to  claim 2  or  4 , wherein the cell is a tumor cell. 
     
     
         6 . A cell differentiation inducer for inducing differentiation of a cell into a regulatory T cell, wherein the inducer activates MCP1 signaling in the cell. 
     
     
         7 . A cell differentiation inducer for inducing differentiation of a cell into a regulatory T cell, comprising a cell expressing a Snail protein, an MCP1 protein, an FSTL1 protein, a membrane IL-13Ra2 protein or a secretory IL-13Ra2 protein. 
     
     
         8 . A cell differentiation inducer for inducing differentiation of a cell into a regulatory T cell, comprising an MCP1 protein, an FSTL1 protein or a secretory IL-13Ra2 protein. 
     
     
         9 . An immunosuppressor, wherein the immunosuppressor activates MCP1 signaling. 
     
     
         10 . An immunosuppressor comprising a cell expressing a Snail protein or a cell expressing an MCP1 protein, an FSTL1 protein, a membrane IL-13Ra2 protein or a secretory IL-13Ra2 protein. 
     
     
         11 . An immunosuppressor comprising an MCP1 protein, an FSTL1 protein or a secretory IL-13Ra2 protein. 
     
     
         12 . An agent for treating hyperimmune disease, wherein the agent activates MCP1 signaling. 
     
     
         13 . An agent for treating hyperimmune disease, comprising a cell expressing a Snail protein, an MCP1 protein, an FSTL1 protein, a membrane IL-13Ra2 protein or a secretory IL-13Ra2 protein. 
     
     
         14 . An agent for treating hyperimmune disease, comprising an MCP1 protein, an FSTL1 protein or a secretory IL-13Ra2 protein. 
     
     
         15 . An inhibitor of enhancement of gene expression for inhibiting enhancement of expression of FoxP3 gene in a cell, wherein the inhibitor suppresses MCP1 signaling in the cell. 
     
     
         16 . An inhibitor of enhancement of gene expression for inhibiting enhancement of expression of FoxP3 gene in a cell, wherein the inhibitor suppresses function of an MCP1 protein, an FSTL1 protein, a membrane IL-13Ra2 protein or a secretory IL-13Ra2 protein. 
     
     
         17 . The inhibitor of enhancement of gene expression according to  claim 15  or  16 , comprising an anti-MCP1 antibody with MCP1 inhibiting activity. 
     
     
         18 . The inhibitor of enhancement of gene expression according to  claim 16 , comprising an anti-FSTL1 antibody with FSTL1 protein inhibiting activity, an anti-membrane IL-13Ra2 antibody with membrane IL-13Ra2 protein inhibiting activity or an anti-secretory IL-13Ra2 antibody with secretory IL-13Ra2 protein inhibiting activity. 
     
     
         19 . An inhibitor of induction of cell differentiation for inhibiting induction of differentiation of a cell into a regulatory T cell, wherein the inhibitor suppresses MCP1 signaling in the cell. 
     
     
         20 . An inhibitor of induction of cell differentiation for inhibiting induction of differentiation of a cell into a regulatory T cell, wherein the inhibitor suppresses function of an MCP1 protein, an FSTL1 protein, a membrane IL-13Ra2 protein or a secretory IL-13Ra2 protein. 
     
     
         21 . The inhibitor of induction of cell differentiation according to  claim 19  or  20 , comprising an anti-MCP1 antibody with MCP1 inhibiting activity. 
     
     
         22 . The inhibitor of induction of cell differentiation according to  claim 20 , comprising an anti-FSTL1 antibody with FSTL1 protein inhibiting activity, an anti-membrane IL-13Ra2 antibody with membrane IL-13Ra2 protein inhibiting activity or an anti-secretory IL-13Ra2 antibody with secretory IL-13Ra2 protein inhibiting activity. 
     
     
         23 . A reducer of immunosuppression suppressing MCP1 signaling. 
     
     
         24 . A reducer of immunosuppression suppressing function of an MCP1 protein, an FSTL1 protein, a membrane IL-13Ra2 protein or a secretory IL-13Ra2 protein. 
     
     
         25 . A reducer of immunosuppression suppressing function of an IL-13 protein, a CCR2 protein or an IL-10 protein. 
     
     
         26 . A stimulator of tumor immunity suppressing MCP1 signaling. 
     
     
         27 . A stimulator of tumor immunity, wherein the stimulator suppresses function of an MCP1 protein, an FSTL1 protein, a membrane IL-13Ra2 protein or a secretory IL-13Ra2 protein. 
     
     
         28 . A stimulator of tumor immunity, wherein the stimulator suppresses function of an IL-13 protein, a CCR2 protein or an IL-10 protein. 
     
     
         29 . An antitumor agent suppressing MCP1 signaling. 
     
     
         30 . An antitumor agent, wherein the agent suppresses function of an MCP1 protein, an FSTL1 protein, a membrane IL-13Ra2 protein or a secretory IL-13Ra2 protein. 
     
     
         31 . An antitumor agent, wherein the agent suppresses function of an IL-13 protein, a CCR2 protein or an IL-10 protein. 
     
     
         32 . A suppressor of tumor growth, wherein the suppressor suppresses MCP1 signaling or function of a TSP1 protein. 
     
     
         33 . A suppressor of tumor cell infiltration, wherein the suppressor suppresses MCP1 signaling or function of an FSTL1 protein. 
     
     
         34 . A suppressor of tumor metastasis, wherein the suppressor suppresses MCP1 signaling or function of an FSTL1 protein. 
     
     
         35 . A gene expression enhancer of FoxP3 gene, MCP1 (monocyte chemoattractant protein-1) gene, TSP1 (thrombospondin-1) gene, FSTL1 (Follistatin-like 1) gene or IL-13Ra2 (interleukin 13 alpha 2 receptor) gene in a cell, comprising a substance enhancing Snail activity. 
     
     
         36 . The gene expression enhancer according to  claim 35 , wherein the substance enhancing Snail activity is an expression vector of a snail gene. 
     
     
         37 . The gene expression enhancer according to  claim 35 , wherein the cell is a Panc-1 cell. 
     
     
         38 . An anticancer agent for blood cancer, comprising an inhibitory substance inhibiting function of a Snail protein. 
     
     
         39 . The anticancer agent according to  claim 38 , wherein the inhibitory substance inhibits expression of the snail gene. 
     
     
         40 . The anticancer agent according to  claim 38  or  39 , wherein the blood cancer is leukemia.