CARBON NANOTUBE COMPOSITIONS AND METHODS OF USE THEREOF
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.
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.