Carbon nanotube compositions and methods of use thereof

• US 8,658,178 B2
• Filed: 03/19/2009
• Issued: 02/25/2014
• Est. Priority Date: 03/19/2008
• Status: Active Grant

• Current Assignee: Yale University
• Original Assignee: Yale University
• Inventors: Fahmy, Tarek M., Pfefferle, Lisa D., Haller, Gary L.
• Primary Examiner(s): JUEDES, AMY E
• Application Number:
  US12/933,223
• Publication Number:
  US 20110014217A1
• Time in Patent Office: 1,804 Days
• Field of Search: None
• US Class Current: 424/193.1
• CPC Class Codes: A61K 2039/542 oral/gastrointestinal
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 47/6925 the form being a microcapsule, nanocapsule, microbubble or nanobubble
• CPC Class Codes: A61K 47/6929 the form being a nanoparticle, e.g. an immuno-nanoparticle
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07K 16/2809 against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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.

Claims

1. An artificial antigen presenting cell composition comprising carbon nanotube bundles comprising

carbon nanotubes attached covalently or non-covalently to one or more T cell receptor activators selected from the group consisting of CD3 antibodies or fragments thereof binding to CD3 or antigens bound to MHC molecules,

wherein the carbon nanotubes are treated with acid prior to adsorption of the one or more T cell receptor activators.

2. The artificial antigen presenting cell composition of claim 1, wherein the carbon nanotubes are single-walled carbon nanotubes.

3. The artificial antigen presenting cell composition of claim 1, wherein the one or more T cell receptor activators are non-covalently bound to the carbon nanotubes by adsorption.

4. The artificial antigen presenting cell composition of claim 1, wherein the T cell receptor activator is an anti-CD3 antibody or fragment thereof.

5. The artificial antigen presenting cell composition of claim 1, wherein the T cell receptor activator comprises MHC molecules bound to peptide antigens.

6. The artificial antigen presenting cell composition of claim 1, further comprising one or more T cell costimulatory or T cell adhesion molecules.

7. The artificial antigen presenting cell composition of claim 1, wherein the antigens bound to MHC molecules are selected from the group consisting of bacterial antigens, viral antigens, tumor antigens, self antigens, and HLA proteins.

8. A method for inducing an immune response comprising

isolating a population of T cells from a subject to be treated,

activating the T cells with an artificial antigen presenting cell composition comprising carbon nanotube bundles comprising carbon nanotubes attached covalently or non-covalently to one or more T cell receptor activators selected from the group consisting of CD3 antibody or fragments thereof binding to CD3 or antigens bound to MHC molecules, wherein the carbon nanotubes are treated with acid prior to adsorption of the one or more T cell receptor activators,

expanding the T cells, and

administering the T cells to the subject to be treated in an amount effective to induce an immune response.

9. The method of claim 8, wherein the subject has a disease or disorder selected from the group consisting of cancer, immunosuppressed conditions, or an infectious disease.

10. A method for reducing 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 an artificial antigen presenting cell composition comprising carbon nanotube bundles comprising carbon nanotubes attached covalently or non-covalently to one or more T cell receptor activators selected from the group consisting of CD3 antibody or fragments thereof binding to CD3 or peptide or protein antigens bound to MHC molecules,

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,

wherein the carbon nanotubes are treated with acid prior to adsorption of the one or more T cell receptor activators.

11. The method of claim 10, wherein the subject has a disease or disorder selected from the group consisting of allergic disease, autoimmune diseases or disorders, graft rejection or graft-versus-host disease.

12. A method for activating T cells comprising administering to a subject in need thereof an effective dose of an artificial antigen presenting cell composition to induce an immune response, the artificial antigen presenting cell composition comprising carbon nanotube bundles comprising carbon nanotubes attached covalently or non-covalently to one or more T cell receptor activators selected from the group consisting of CD3 antibody or fragments thereof binding to CD3 or antigens bound to MHC molecules, wherein the carbon nanotubes are treated with acid prior to adsorption of the one or more T cell receptor activators.