Carbon nanotube compositions and methods of use thereof

Abstract

Carbon nanotube (CNT)-based compositions for activating cellular immune responses are provided. The CNTs function as high surface area scaffolds for the attachment of T cell ligands and/or antigens. The CNT compositions function as artificial antigen-presenting cells (aAPCs) or as modular vaccines. The disclosed CNT aAPCs are efficient at activating T cells and may be used to activate T cells ex vivo or in vivo for adoptive or active immunotherapy.

We claim: 
     
         1 . A nanotube particle composite comprising carbon nanotubes,
 the nanotubes having bound to or present on the surface one or more T cell receptor activators and nanoparticles comprising an immunostimulatory agent.   
     
     
         2 . The nanotube particle composite of  claim 1 , wherein the carbon nanotubes are single-walled carbon nanotubes. 
     
     
         3 . The nanotube particle composite of  claim 1 , wherein the one or more T cell receptor activators are non-covalently bound to the carbon nanotubes by adsorption. 
     
     
         4 . The nanotube particle composite of  claim 1 , wherein the carbon nanotubes are treated with acid prior to adsorption of the one or more T cell receptor activators. 
     
     
         5 . The nanotube particle composite of  claim 1 , wherein the T cell receptor activator is a polyclonal T cell activator. 
     
     
         6 . The nanotube particle composite of  claim 1 , wherein the T cell receptor activator comprises MHC molecules bound to peptide antigens. 
     
     
         7 . The nanotube particle composite of  claim 1 , wherein the nanoparticle further comprises a biodegradable polymer. 
     
     
         8 . The nanotube particle composite of  claim 9 , wherein the biodegradable polymer is selected from the group consisting of ferromagnetica and superparamagnetic materials. 
     
     
         9 . The nanotube particle composite of  claim 8 , wherein the polymer is polylactic acid, polyglycolic acid, or polylactide-co-glycolide. 
     
     
         10 . The nanotube particle composite of  claim 1 , further comprising a magnetic particle. 
     
     
         11 . The nanotube particle composite of  claim 10 , wherein the magnetic particle is present on or encapsulated in the nanoparticle. 
     
     
         12 . The nanotube particle composite of  claim 10 , wherein the magnetic particle is selected from the group consisting of ferromagnetic and superparamagnetic materials. 
     
     
         13 . The nanotube particle composite of  claim 11 , wherein the magnetic particle is magnetite. 
     
     
         14 . The nanotube particle composite of  claim 1 , wherein the immunostimulatory agent is IL-2. 
     
     
         15 . A method for adoptive immunotherapy of a disease or disorder comprising
 isolating a population of T cells from a subject to be treated,   activating the T cells with a nanotube particle composite comprising carbon nanotubes, the nanotubes having bound to or present on the surface one or more T cell receptor activators and a nanoparticle comprising an immunostimulatory agent,   expanding the T cells, and   administering the T cells to the subject to be treated in an amount effective to induce an immune response.   
     
     
         16 . The method of  claim 15 , wherein the disease or disorder is selected from the group consisting of cancer, immunosuppressed conditions, or infectious disease. 
     
     
         17 . The method of  claim 15 , wherein the nanotube particle composite further comprises a magnetic particle, and
 wherein the method further comprises separating the T cells from the nanotube particle composite prior to administering them to the subject to be treated.   
     
     
         18 . A method for adoptive immunotherapy of a disease or disorder characterized by over-activation, undesirable or aberrant activation of an immune response comprising
 isolating a population of CD4 + CD45 +  T cells from a subject to be treated,   activating the CD4 + CD45 +  T cells with the nanotube particle composite of  claim 1 ,   expanding the CD4 + CD45 +  T cells, and   administering the CD4 + CD45 +  T cells to the subject to be treated in an amount effective to eliminate or reduce the risk or delay the outset of conditions associated with undesirable activation, over-activation or inappropriate or aberrant activation of an immune response.   
     
     
         19 . The method of  claim 18 , wherein the disease or disorder is selected from the group consisting of allergic disease, autoimmune diseases or disorders, graft rejection or graft-versus-host disease. 
     
     
         20 . The method of  claim 18 , wherein the nanotube particle composite further comprises a magnetic particle, and
 wherein the method further comprises separating the CD4 + CD45 +  T cells from the nanotube particle composite prior to administering them to the subject to be treated.   
     
     
         21 . A method for active immunotherapy of a disease or disorder comprising
 administering to a subject in need thereof an effective dose of a nanotube particle composite comprising carbon nanotubes, the nanotubes having bound to or present on the surface one or more T cell receptor activators and a nanoparticle comprising an immunostimulatory agent, to induce an immune response.   
     
     
         22 . The method of  claim 21 , wherein the disease or disorder is cancer, and wherein the modular vaccine composition is administered in an effective amount to delay or inhibit tumor growth.