Nanoparticle Based Artificial Antigen Presenting Cell Mediated Activation of NKT Cells

Patent metadata

Field	Value
Publication number	US-2016237137-A1
Application number	US-201415027148-A
Country	US
Kind code	A1
Filing date	Oct 3, 2014
Priority date	Oct 3, 2013
Publication date	Aug 18, 2016
Grant date	—

Abstract

The present invention relates to, in part, artificial antigen presenting cells that are useful in treating disease (including cancers) and have uses, for example, directly in vivo and/or in the expansion of a patients cells for re-introduction ex vivo.

First claim

1 . A microparticle or nanoparticle, comprising on its surface:
(a) a population of antigen presenting complexes that activate T cell receptors (TCRs) of NKT cells and (b) a population of NKT cell costimulatory ligands.

2 . The microparticle or nanoparticle of claim 1 , wherein the molecule capable of interacting with one or more T cell receptors (TCRs) of a NKT cell is CD1d, or antigen presenting fragment thereof.

3 . The microparticle or nanoparticle of claim 2 , wherein the CD1d is a fusion protein with immunoglobulin sequences.

4 . The microparticle or nanoparticle of claim 3 , wherein the CD1d is fused with an immunoglobulin heavy chain sequence, or fragment thereof, thereby providing a dimeric CD1d ligand.

5 . The microparticle or nanoparticle of claim 2 , wherein the molecule capable of interacting with one or more T cell receptors (TCRs) of a NKT cell comprises an NKT cell antigen.

6 . The microparticle or nanoparticle of claim 5 , wherein the antigen is a lipid or glycolipid antigen.

7 . The microparticle or nanoparticle of claim 6 , wherein the antigen is one or more of α-GalCer, α-C-GalCer, -OCH, GSL-1, and iGB3.

8 . The microparticle or nanoparticle of claim 1 , wherein the NKT cell costimulatory ligands is an antibody or antigen-binding fragment thereof that specifically binds to one or more of CD28, CD44, CD40, and CD161.

9 . The microparticle or nanoparticle of claim 8 , wherein the antibody or antigen-binding fragment is selected from a monoclonal antibody, a F(ab′)2, a Fab, scFv, or a single chain antibody.

10 . The microparticle or nanoparticle of claim 3 , wherein the immunoglobulin sequence and/or antibody or antigen-binding fragment comprise a fully human or humanized sequence.

11 . The microparticle or nanoparticle of claim 1 , wherein the microparticle or nanoparticle is paramagnetic.

12 . The microparticle or nanoparticle of claim 11 , wherein the paramagnetic bead comprises an iron dextran bead.

13 . The microparticle or nanoparticle of claim 12 , wherein the bead or particle is a quantum dot.

14 . The microparticle or nanoparticle of claim 1 , wherein the microparticle or nanoparticle has a size of within about 10 to about 500 nm.

15 . The microparticle or nanoparticle of claim 1 , wherein the microparticle or nanoparticle is substantially spherical.

16 . The microparticle or nanoparticle of claim 1 , wherein the population of antigen presenting complexes and the co-stimulatory ligands is covalently bound to the surface of the microparticle or nanoparticle.

17 . The microparticle or nanoparticle of claim 1 , wherein the microparticle or nanoparticle is suitable for antigen presentation.

18 . The microparticle or nanoparticle of claim 1 , wherein the microparticle or nanoparticle is suitable for stimulating NKT cells.

19 . The microparticle or nanoparticle of claim 1 , wherein the NKT cells are Type I and/or Type II NKT cells.

20 . The microparticle or nanoparticle of claim 18 , wherein the NKT cells are CD4+, CD8+, or CD4+CD8+, CD4−CD8−.

21 .- 43 . (canceled)

Assignees

• Univ Maryland

Inventors

• Webb Tonya
• Morris Carolyn
• East James

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K16/00

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K14/70539 Primary

  MHC-molecules, e.g. HLA-molecules · CPC title

• A61K49/1875

  coated or functionalised with an antibody · CPC title