Targeting of antigen presenting cells with immunonanotherapeutics

• US 9,308,280 B2
• Filed: 10/04/2013
• Issued: 04/12/2016
• Est. Priority Date: 10/12/2008
• Status: Active Grant

• Current Assignee: Brigham and Women's Hospital Incorporated, President and Fellows of Harvard College (Harvard Corporation), Massachusetts Institute of Technology
• Original Assignee: Brigham and Women's Hospital Incorporated, President and Fellows of Harvard College (Harvard Corporation), Massachusetts Institute of Technology
• Inventors: Shi, Jinjun, Alexis, Frank, Iannacone, Matteo, Moseman, Elliott Ashley, Basto, Pamela, Langer, Robert S., Farokhzad, Omid C., von Andrian, Ulrich H., Tonti, Elena
• Primary Examiner(s): NAVARRO, ALBERT MARK
• Application Number:
  US14/046,827
• Publication Number:
  US 20140037736A1
• Time in Patent Office: 921 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 47/6925 the form being a microcapsule, nanocapsule, microbubble or nanobubble
• CPC Class Codes: A61K 47/6935 the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection

Abstract

The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides nanocarriers capable of stimulating an immune response in T cells and/or in B cells. The invention provides nanocarriers that comprise an immunofeature surface. The nanocarriers are capable of targeting antigen presenting cells when administered to a subject. The invention provides pharmaceutical compositions comprising inventive nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive nanocarriers and pharmaceutical compositions thereof.

Claims

1. A composition comprising:

(a) polymeric particles formed from the self-assembly of a mixture of amphiphilic (hydrophobic-hydrophilic) polymers and amphiphilic polymers having at least one moiety bound to the hydrophilic ends of the amphiphilic polymers;

(b) a B cell or T cell antigen;

(c) an immunostimulatory agent to promote tolerance to the antigen; and

(d) a pharmaceutically acceptable excipient.

2. The composition of claim 1, wherein the surface of the polymeric particle further comprises a targeting moiety.

3. The composition of claim 1, wherein the polymeric particles further comprise an immunomodulatory agent.

4. The composition of claim 3, wherein the immunostimulatory agent, or antigen is (i) on the surface of the polymeric particle;

or (ii) encapsulated within the polymeric particle.

5. The composition of claim 1, wherein the diameter of the polymeric particles is greater than 100 nm.

6. The composition of claim 1, wherein the pharmaceutically acceptable excipient is selected from solvents, dispersion media, diluents, or other liquid vehicles, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, solid binders, and lubricants.

7. The composition of claim 1, wherein the composition targets a subcapsular sinus macrophage.

8. The composition of claim 1, wherein the composition targets a dendritic cell.

9. The composition of claim 1, wherein the composition does not substantially activate complement.

10. The composition of claim 1, wherein a first surface of the polymeric particles comprises a plurality of B cell antigen in an amount effective to provide a humoral response to the B cell antigen.

11. The composition of claim 10, wherein the composition does not substantially activate complement.

12. The composition of claim 1, wherein the polymeric particle comprises biodegradable polymers.

13. The composition of claim 1, wherein the polymeric particle comprises a biocompatible polymer that is a conjugate of a water soluble, non-adhesive polymer and a biodegradable hydrophobic polymer.

14. The composition of claim 13, wherein the biocompatible polymer is polyethylene glycol-poly(lactic acid-co-glycolic acid) (PEG-PLGA).

15. The composition of claim 1, wherein the polymeric particle comprises a conjugate of a polymer and a moiety selected from the group consisting of antigens, immunostimulatory agents, and targeting moieties.

16. The composition of claim 1, wherein the polymeric particle comprises polymers having the formula X-L1-Y-L2-Z, wherein

X is a biodegradable hydrophobic polymer,

Y is a water soluble, non-adhesive polymer,

Z is selected from the group consisting of targeting moieties, immunomodulatory agents, immunostimulatory agents, and therapeutic or diagnostic agents, and

L1 and L2 are bonds or linking molecules.

17. The composition of claim 1, wherein the polymeric particle comprises a molecule having the formula T-L1-X-L2-Y-L3-Z, wherein

T is a T cell antigen,

X is a biodegradable hydrophobic polymer,

Y is a water soluble, non-adhesive polymer,

Z is selected from the group consisting of targeting moieties, immunomodulatory agents, immunostimulatory agents, and therapeutic or diagnostic agents, and

L1, L2, and L3 are bonds or linking molecules.

18. The composition of claim 12 wherein the biodegradable polymer is selected from the group consisting of polylactic acid (PLA), poly(glycolic acid) (PGA), and poly(lactic acid/glycolic acid) (PLGA).

19. The composition of claim 13, wherein the water soluble, non-adhesive polymer is selected from the group consisting of polyethylene glycol (PEG), polyethylene oxide (PEO), and copolymers thereof.

20. The composition of claim 1, wherein the polymeric particles are selected from the group consisting of microparticles and nanoparticles.

21. The composition of claim 1, wherein the immunostimulatory agent is an immunosuppressant or induces regulatory T cells.

22. The composition of claim 20, wherein the immunosuppressant is selected from the group consisting of cyclosporin, a steroid, methotrexate, and agent that interferes with T cell activation.

23. The composition of claim 20, wherein the immunostimulatory agent that induces regulatory T cells is selected from the group consisting of TGF-β

, rapamycin or retinoic acid.