Artificial antigen presenting cells having a defined and dynamic shape
Compositions and methods comprising asymmetrical artificial antigen presenting cells (aAPCs) are disclosed. The non-spherical aAPCs more closely mimic endogenous cell-cell interactions and can be used for antigen-specific immunotherapy.
1. An artificial antigen presenting cell (aAPC) that is a biodegradable, polymeric three-dimensional microparticle or nanoparticle having a non-spherical ellipsoidal shape that mimics a shape of a cell or a microorganism and comprises one or more molecules capable of interacting with one or more T cell receptors (TCRs) of a T cell and a molecule capable of interacting with a receptor or ligand on the T cell other than TCRs;
wherein the microparticle or the nanoparticle has an aspect ratio ranging from about 1.1 to about 5, wherein the aspect ratio is determined by dividing a diameter of a long axis of the non-spherical ellipsoidal shape of the microparticle or nanoparticle by a diameter of a short axis of the non-spherical ellipsoidal shape of the microparticle or nanoparticle; and
wherein the non-spherical ellipsoidal shape has at least one surface having a radius of curvature along at least one axis selected from one of the following ranges: (a) about 1 nm to about 10 nm; (b) about 11 nm to about 100 nm; (c) about 101 nm to about 400 nm; (d) about 401 nm to about 1 μm; (e) about 10 μm to about 20 μm; (f) about 20 μm to about 100 μm; and (g) about 101 μm to about 1 mm.
2. The aAPC of claim 1 , wherein the cell or the microorganism is selected from the group consisting of a bacterium, an archaeon, a protozoan, a fungus, an algae, and a virus.
3. The aAPC of claim 1 wherein the non-spherical ellipsoidal shape is defined by a dimension (a) along an x-axis, a dimension (b) along a y-axis, and a dimension (c) along a z-axis, wherein at least one of (a), (b), or (c) is not equal to at least one other dimension (a), (b), or (c).
4. The aAPC of claim 3 , wherein the three-dimensional microparticle or the nanoparticle comprises an ellipsoid selected from the group consisting of:
a prolate ellipsoid, wherein the dimension (a) along the x-axis is greater than the dimension (b) along the y-axis, and wherein the dimension (b) along the y-axis is equal to the dimension (c) along the z-axis, such that the prolate ellipsoid can be described by the equation a>b=c;
a tri-axial ellipsoid, wherein the dimension (a) along the x-axis is greater than the dimension (b) along the y-axis, and wherein the dimension (b) along the y-axis is greater than the dimension (c) along the z-axis, such that the tri-axial ellipsoid can be described by the equation a >b >c; and
an oblate ellipsoid, wherein the dimension (a) along the x-axis is equal to the dimension (b) along the y-axis, and wherein the dimension (b) along the y-axis is greater than the dimension (c) along the z-axis, such that the oblate ellipsoid can be described by the equation a=b >c.
5. The aAPC of claim 3 , wherein the dimension (a) along the x axis is equal to the dimension (b) along the y axis, both of which are much less than dimension (c) along the z-axis, such that the three-dimensional microparticle or the nanoparticle comprises a rod.
6. The aAPC of claim 1 , wherein the three-dimensional microparticle or the nanoparticle comprises a material having one or more of the following characteristics:
(i) one or more degradable linkages;
(ii) a stretchable modulus; and
(iii) a glass transition temperature such that the material comprising the three-dimensional microparticle or the nanoparticle is a solid at a temperature selected from at least one of room temperature and body temperature.
7. The aAPC of claim 6 , wherein the degradable linkage is selected from the group consisting of an ester linkage, a disulfide linkage, an amide linkage, an anhydride linkage, and a linkage susceptible to enzymatic degradation.
8. The aAPC of claim 1 , wherein the biodegradable polymer or blends of polymers is(are) selected from the group consisting of poly(lactic-co-glycolic acid) (PLGA), poly(beta-amino ester) (PBAE), polycaprolactone (PCL), polyglycolic acid (PGA), polylactic acid (PLA), poly(acrylic acid) (PAA), poly-3-hydroxybutyrate (P3HB), and poly(hydroxybutyrate-co-hydroxyvalerate).
9. The aAPC of claim 8 , wherein the biodegradable polymer or the blends of polymers are blended with a nondegradable polymer.
10. The aAPC of claim 1 , wherein the molecule capable of interacting with the TCR is a peptide.
11. The aAPC of claim 10 , wherein the peptide is loaded onto a MHC-Ig molecule or a HLA:Ig molecule before interacting with the TCR.
12. The aAPC of claim 1 , wherein the receptor on the T cell other than TCRs is selected from the group consisting of CD28, CD2, CD5, CD44, OX40, 4-1BBL, ICAM-1, and LFA-1.
13. The aAPC of claim 12 , wherein the receptor on the T cell other than TCRs is CD28.
14. The aAPC of claim 13 , wherein the CD28 receptor interacts with an anti-CD28 antibody or a B7 protein.
15. The aAPC of claim 1 , further comprising a drug or a therapeutic agent.
16. The aAPC of claim 15 , wherein the drug or the therapeutic agent is a protein.
17. The aAPC of claim 1 , further comprising at least one peptide or protein found on at least one of a surface of the aAPC or within the aAPC.
18. A kit comprising the aAPC of claim 1 .