Nanoparticle based artificial antigen presenting cell mediated activation of NKT cells
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.
1. A microparticle or nanoparticle artificial antigen presenting cell for stimulation and expansion of NKT cells, comprising:
(a) a paramagnetic iron dextran bead; and, on the surface of the bead,
(b) a population of CD1d antigen presenting complexes that activate T cell receptors (TCRs) of natural killer T (NKT) cells, wherein the CD1d antigen presenting complexes present an NKT cell antigen selected from the group consisting of α-C-GalCer, GSL-1, and iGB3;
(c) a population of NKT cell costimulatory ligands which specifically bind to CD44;
(d) a population of NKT cell costimulatory ligands which specifically bind to CD161;
(e) a population of binding NKT cell costimulatory ligands which specifically bind to CD28 and a population of NKT cell costimulatory ligands which specifically bind to CD40,
wherein the NKT cell costimulatory ligands are antibodies or antigen-binding fragments thereof,
wherein the CD1d antigen is a fusion protein with an immunoglobulin sequence,
wherein the ratio of CD1d-Ig to anti-CD28 is 10:1,
wherein the microparticle or nanoparticle artificial antigen presenting cell has a size of 150 nm or 200 nm.
2. A microparticle or nanoparticle artificial antigen presenting cell for stimualation and expansion of NKT cells, consisting essentially of:
(a) a paramagnetic iron dextran bead; and, on the surface of the bead,
(b) a population of CD1d antigen presenting complexes that activate T cell receptors (TCRs) of natural killer T (NKT) cells, wherein the CD1d antigen presenting complexes present an NKT cell antigen selected from the group consisting of a-C-GalCer, GSL-1, and iGB3;
(c) a population of NKT cell costimulatory ligands which specifically bind to CD44;
(d) a population of NKT cell costimulatory ligands which specifically bind to CD161;
(e) a population of binding NKT cell costimulatory ligands which specifically bind to CD28 and a population of NKT cell costimulatory ligands which specifically bind to CD40,
wherein the NKT cell costimulatory ligands are antibodies or antigen-binding fragments thereof,
wherein the CD1d antigen is a fusion protein with an immunoglobulin sequence,
wherein the ratio of CD 1 d-Ig to NKT cell costimulatory CD28-binding ligand is 10:1,
wherein the microparticle or nanoparticle artificial antigen presenting cell has a size of 150 nm or 200 nm.
3. The microparticle or nanoparticle artificial antigen presenting cell of claim 1 , wherein the CD1d antigen presenting complexes are fused with an immunoglobulin heavy chain sequence, or fragment thereof, thereby providing a dimeric CD1d ligand.
4. The microparticle or nanoparticle artificial antigen presenting cell of claim 2 , wherein the CD1d antigen presenting complexes are fused with an immunoglobulin heavy chain sequence, or fragment thereof, thereby providing a dimeric CD1d ligand.
5. The microparticle or nanoparticle artificial antigen presenting cell of claim 1 , wherein the NKT cells are Type I and/or Type II NKT cells.
6. The microparticle or nanoparticle artificial antigen presenting cell of claim 2 , wherein the NKT cells are Type I and/or Type II NKT cells.
7. The microparticle or nanoparticle artificial antigen presenting cell of claim 1 , wherein the NKT cells are CD4+, CD8+, or CD4+CD8+, CD4−CD8−.
8. The microparticle or nanoparticle artificial antigen presenting cell of claim 2 , wherein the NKT cells are CD4+, CD8+, or CD4+CD8+, CD4−CD8−.
9. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the microparticle or nanoparticle artificial antigen presenting cell of claim 1 .
10. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the microparticle or nanoparticle artificial antigen presenting cell of claim 2 .