Chimeric antigen receptor anti-inflammatory cells and methods of use

Abstract

A nucleic acid construct and an immune cell, which harbor nucleic acids encoding a CAR and nucleic acids encoding at least one anti-inflammatory or immunosuppressant protein and methods of using the same in treatment or amelioration of inflammation or immune-mediated autoimmunity are described.

What is claimed is: 
     
         1 . An immune cell comprising nucleic acids encoding a chimeric antigen receptor and nucleic acids encoding at least one exogenous anti-inflammatory or immunosuppressant protein. 
     
     
         2 . The immune cell of  claim 1 , wherein the cell is a T lymphocyte-. 
     
     
         3 . The immune cell of  claim 1 , wherein the chimeric antigen receptor comprises a single chain variable fragment-. 
     
     
         4 . The immune cell of  claim 1 , wherein the chimeric antigen receptor comprises an antigen targeting domain or recognition domain that binds an antigen or ligand at a site of inflammation or autoimmunity and an immune signaling receptor containing an immunoreceptor tyrosine-based activation motif. 
     
     
         5 . The immune cell of  claim 3 , wherein the chimeric antigen receptor further comprises a costimulatory endodomain-. 
     
     
         6 . The immune cell of  claim 1 , wherein the antiinflammatory or immunosuppressant protein comprises a cytokine, virokine or a C-type lectin protein. 
     
     
         7 . The immune cell of  claim 6 , wherein the virokine is a viral IL-10 protein. 
     
     
         8 . The immune cell of  claim 6 , wherein the C-type lectin protein is a helminth C-type lectin protein. 
     
     
         9 . The immune cell of  claim 1 , wherein expression of the anti-inflammatory or immunosuppressant protein is regulated by a promoter that is dependent upon signaling from the chimeric antigen receptor. 
     
     
         10 . A nucleic acid construct comprising nucleic acids encoding a chimeric antigen receptor and nucleic acids encoding at least one anti-inflammatory or immunosuppressant protein. 
     
     
         11 . The nucleic acid construct of  claim 10 , wherein the construct comprises a vector. 
     
     
         12 . The nucleic acid construct of  claim 10 , wherein the chimeric antigen receptor comprises a single chain variable fragment. 
     
     
         13 . The nucleic acid construct of  claim 10 , wherein the chimeric antigen receptor comprises an antigen targeting domain or recognition domain that binds a ligand at a site of inflammation or autoimmunity and an immune signaling receptor containing an immunoreceptor tyrosine-based activation motif. 
     
     
         14 . The nucleic acid construct of  claim 12 , wherein the chimeric antigen receptor further comprises a costimulatory endodomain. 
     
     
         15 . The nucleic acid construct of  claim 10 , wherein the anti-inflammatory or immunosuppressant protein comprises a cytokine, virokine or a C-type lectin protein. 
     
     
         16 . The nucleic acid construct of  claim 15 , wherein the virokine is a viral IL-10 protein. 
     
     
         17 . The nucleic acid construct of  claim 15 , wherein the C-type lectin protein is a helminth C-type lectin protein-. 
     
     
         18 . The nucleic acid construct of  claim 10 , wherein expression of the anti-inflammatory or immunosuppressant protein is regulated by a promoter that is enhanced upon signaling from the chimeric antigen receptor. 
     
     
         19 . A method for treating inflammation or immune-mediated autoimmunity comprising delivering to a subject in need of treatment an effective amount of immune cell of  claim 1  thereby treating the subject's inflammation or immune-mediated autoimmunity. 
     
     
         20 . A kit comprising one or more immune cells of  claim 1 . 
     
     
         21 . (canceled)