Size-tunable synthetic particles with tunable optical properties and methods for using the same for immune cell activation
A hydrogel particle, comprising a matrix comprising a polymerized monomer, said matrix comprising a plurality of micropores and a plurality of macropores, and one or more immunostimulatory biomolecules selected from the group consisting of an anti-CD3 antibody or antigen-binding fragment thereof, an anti-CD28 antibody or antigen-binding fragment thereof, and combinations thereof.
1 . A particle for inducing an immune cell response, the particle comprising:
a matrix comprising a polymerized monomer having a plurality of micropores and a plurality of macropores; and
one or more immunostimulatory or co-stimulatory biomolecules,
wherein the plurality of macropores comprise an average diameter between about 200 nm and about 2 μm, wherein the particle is capable of inducing the immune cell response when contacted with an immune cell, and wherein the immune cell response comprises activation and/or expansion of the immune cell.
2 . The particle of claim 1 , wherein an average diameter of the plurality of micropores is between about 1 nm and about 20 nm.
3 . The particle of claim 1 , wherein the average diameter of the plurality of micropores is between about 2 nm and about 4 nm.
4 . The particle of claim 1 , wherein the immune cell response from contacting the immune cell with the particle is higher than the immune cell response from a control immune cell contacted with an otherwise identical particle lacking the plurality of macropores.
5 . The particle of claim 4 , wherein the immune cell response is determined by IL-2 secretion, CD25 expression, or CD69 expression, from the immune cell.
6 . The particle of claim 1 , wherein the immune cell is a T cell.
7 . The particle of claim 1 , wherein the immune cell is a cytotoxic T cell.
8 . The particle of claim 1 , wherein the immune cell is a chimeric antigen receptor (CAR) T cell.
9 . The particle of claim 1 , wherein the particle has a porosity of about 5% to about 95% of a volume of the particle.
10 . The particle of claim 1 , wherein the one or more immunostimulatory or co-stimulatory biomolecules are attached to a surface of the matrix via a linker.
11 . The particle of claim 10 , wherein the linker comprises streptavidin.
12 . The particle of claim 1 , wherein the one or more immunostimulatory or co-stimulatory biomolecules are biotinylated.
13 . The particle of claim 1 , wherein the matrix comprises a bifunctional monomer and wherein the one or more immunostimulatory or co-stimulatory biomolecules are attached to the bifunctional monomer.
14 . The particle of claim 1 , wherein the one or more immunostimulatory or co-stimulatory biomolecules are selected from the group consisting of an anti-CD3 antibody or antigen-binding fragment thereof, an anti-CD28 antibody or antigen-binding fragment thereof, an anti-CD19 antibody or antigen-binding fragment, an anti-41BBL antibody or antigen-binding fragment, an anti-OX40L antibody or antigen-binding fragment, an anti-CD2 antibody or antigen-binding fragment, an anti-CD335 antibody or antigen-binding fragment, an anti-CD16 antibody or antigen-binding fragment, an anti-CD56 antibody or antigen-binding fragment, an anti-CD20 antibody or antigen-binding fragment, an anti-CD80 antibody or antigen-binding fragment, an anti-CD86 antibody or antigen-binding fragment, an anti-CD69 antibody or antigen-binding fragment, an anti-CD154 antibody or antigen-binding fragment, an anti-CD137 antibody or antigen-binding fragment, an IgM antibody or antigen-binding fragment, an IgG antibody or antigen-binding fragment, an IgE antibody or antigen-binding fragment, an IgA antibody or antigen-binding fragment, an IgD antibody or antigen-binding fragment, a toll-like receptor, and any combination thereof.
15 . The particle of claim 1 , wherein the one or more immunostimulatory or co-stimulatory biomolecules are selected from the group consisting of anti-CD19, anti-41BBL, anti-OX40L, anti-CD2, anti-CD335, anti-CD16, anti-CD56, anti-CD20, anti-CD80, anti-CD86, anti-CD69, anti-CD154, anti-CD137, and any combination thereof.
16 . The particle of claim 1 , wherein the one or more immunostimulatory or co-stimulatory biomolecules comprise:
an anti-CD3 antibody or an antigen-binding fragment thereof; and/or
an anti-CD28 antibody or an antigen-binding fragment thereof.
17 . The particle of claim 1 , wherein the plurality of micropores are formed during monomer polymerization.
18 . The particle of claim 1 , wherein the plurality of macropores comprise between about 2% and about 30% of a total number of pores of the particle, the total number of pores of the particle being a combination of the plurality of micropores and the plurality of macropores.
19 . The particle of claim 1 , wherein the particle comprises the plurality of macropores at a concentration of at least about 2.25% v/v.
20 . The particle of claim 1 , wherein the particle has a diameter between about 1 μm and about 25 μm.
21 . The particle of claim 20 , wherein the particle has a diameter between about 2 μm and about 5 μm.
22 . A particle for inducing an immune cell response, the particle comprising:
a matrix comprising a polymerized monomer having a plurality of micropores and a plurality of macropores; and
one or more immunostimulatory or co-stimulatory biomolecules,
wherein the particle is capable of inducing the immune cell response when contacted with an immune cell, wherein the immune cell response comprises activation and/or expansion of the immune cell, and wherein the immune cell response from contacting the immune cell with the particle is higher than the immune cell response from a control immune cell contacted with an otherwise identical particle lacking the plurality of macropores.
23 . The particle of claim 22 , wherein an average diameter of the plurality of micropores is between about 1 nm and about 20 nm.
24 . The particle of claim 22 , wherein the average diameter of the plurality of micropores is between about 2 nm and about 4 nm.
25 . The particle of claim 22 , wherein the immune cell response is determined by IL-2 secretion, CD25 expression, or CD69 expression, from the immune cell.
26 . The particle of claim 22 , wherein the immune cell is a T cell.
27 . The particle of claim 22 , wherein the immune cell is a cytotoxic T cell.
28 . The particle of claim 22 , wherein the immune cell is a chimeric antigen receptor (CAR) T cell.
29 . The particle of claim 22 , wherein the particle has a porosity of about 5% to about 95% of a volume of the particle.
30 . The particle of claim 22 , wherein the one or more immunostimulatory or co-stimulatory biomolecules are attached to a surface of the matrix via a linker.
31 . The particle of claim 30 , wherein the linker comprises streptavidin.
32 . The particle of claim 22 , wherein the one or more immunostimulatory or co-stimulatory biomolecules are biotinylated.
33 . The particle of claim 22 , wherein the matrix comprises a bifunctional monomer and wherein the one or more immunostimulatory or co-stimulatory biomolecules are attached to the bifunctional monomer.
34 . The particle of claim 22 , wherein the one or more immunostimulatory or co-stimulatory biomolecules are selected from the group consisting of an anti-CD3 antibody or antigen-binding fragment thereof, an anti-CD28 antibody or antigen-binding fragment thereof, an anti-CD19 antibody or antigen-binding fragment, an anti-41BBL antibody or antigen-binding fragment, an anti-OX40L antibody or antigen-binding fragment, an anti-CD2 antibody or antigen-binding fragment, an anti-CD335 antibody or antigen-binding fragment, an anti-CD16 antibody or antigen-binding fragment, an anti-CD56 antibody or antigen-binding fragment, an anti-CD20 antibody or antigen-binding fragment, an anti-CD80 antibody or antigen-binding fragment, an anti-CD86 antibody or antigen-binding fragment, an anti-CD69 antibody or antigen-binding fragment, an anti-CD154 antibody or antigen-binding fragment, an anti-CD137 antibody or antigen-binding fragment, an IgM antibody or antigen-binding fragment, an IgG antibody or antigen-binding fragment, an IgE antibody or antigen-binding fragment, an IgA antibody or antigen-binding fragment, an IgD antibody or antigen-binding fragment, a toll-like receptor, and any combination thereof.
35 . The particle of claim 22 , wherein the one or more immunostimulatory or co-stimulatory biomolecules are selected from the group consisting of anti-CD19, anti-41BBL, anti-OX40L, anti-CD2, anti-CD335, anti-CD16, anti-CD56, anti-CD20, anti-CD80, anti-CD86, anti-CD69, anti-CD154, anti-CD137, and any combination thereof.
36 . The particle of claim 22 , wherein the one or more immunostimulatory or co-stimulatory biomolecules comprise:
an anti-CD3 antibody or an antigen-binding fragment thereof; and/or
an anti-CD28 antibody or an antigen-binding fragment thereof.
37 . The particle of claim 22 , wherein the plurality of micropores are formed during monomer polymerization.
38 . The particle of claim 22 , wherein the plurality of macropores comprise between about 2% and about 30% of a total number of pores of the particle, the total number of pores of the particle being a combination of the plurality of micropores and the plurality of macropores.
39 . The particle of claim 22 , wherein the particle comprises the plurality of macropores at a concentration of at least about 2.25% v/v.
40 . The particle of claim 22 , wherein the particle has a diameter between about 1 μm and about 25 μm.
41 . The particle of claim 40 , wherein the particle has a diameter between about 2 μm and about 5 μm.
42 . A particle for inducing an immune cell response, the particle comprising:
a matrix comprising a polymerized monomer having a plurality of micropores and a plurality of macropores; and
one or more immunostimulatory or co-stimulatory biomolecules,
wherein the particle is capable of inducing the immune cell response when contacted with an immune cell, wherein the immune cell response comprises activation and/or expansion of the immune cell, and wherein the plurality of micropores are formed during monomer polymerization.
43 . The particle of claim 42 , wherein an average diameter of the plurality of micropores is between about 1 nm and about 20 nm.
44 . The particle of claim 42 , wherein the average diameter of the plurality of micropores is between about 2 nm and about 4 nm.
45 . The particle of claim 42 , wherein the immune cell response from contacting the immune cell with the particle is higher than the immune cell response from a control immune cell contacted with an otherwise identical particle lacking the plurality of macropores, and wherein the immune cell response is determined by IL-2 secretion, CD25 expression, or CD69 expression, from the immune cell.
46 . The particle of claim 42 , wherein the immune cell is a T cell.
47 . The particle of claim 42 , wherein the immune cell is a cytotoxic T cell.
48 . The particle of claim 42 , wherein the immune cell is a chimeric antigen receptor (CAR) T cell.
49 . The particle of claim 42 , wherein the particle has a porosity of about 5% to about 95% of a volume of the particle.
50 . The particle of claim 42 , wherein the one or more immunostimulatory or co-stimulatory biomolecules are attached to a surface of the matrix via a linker.
51 . The particle of claim 50 , wherein the linker comprises streptavidin.
52 . The particle of claim 42 , wherein the one or more immunostimulatory or co-stimulatory biomolecules are biotinylated.
53 . The particle of claim 42 , wherein the matrix comprises a bifunctional monomer and wherein the one or more immunostimulatory or co-stimulatory biomolecules are attached to the bifunctional monomer.
54 . The particle of claim 42 , wherein the one or more immunostimulatory or co-stimulatory biomolecules are selected from the group consisting of an anti-CD3 antibody or antigen-binding fragment thereof, an anti-CD28 antibody or antigen-binding fragment thereof, an anti-CD19 antibody or antigen-binding fragment, an anti-41BBL antibody or antigen-binding fragment, an anti-OX40L antibody or antigen-binding fragment, an anti-CD2 antibody or antigen-binding fragment, an anti-CD335 antibody or antigen-binding fragment, an anti-CD16 antibody or antigen-binding fragment, an anti-CD56 antibody or antigen-binding fragment, an anti-CD20 antibody or antigen-binding fragment, an anti-CD80 antibody or antigen-binding fragment, an anti-CD86 antibody or antigen-binding fragment, an anti-CD69 antibody or antigen-binding fragment, an anti-CD154 antibody or antigen-binding fragment, an anti-CD137 antibody or antigen-binding fragment, an IgM antibody or antigen-binding fragment, an IgG antibody or antigen-binding fragment, an IgE antibody or antigen-binding fragment, an IgA antibody or antigen-binding fragment, an IgD antibody or antigen-binding fragment, a toll-like receptor, and any combination thereof.
55 . The particle of claim 42 , wherein the one or more immunostimulatory or co-stimulatory biomolecules are selected from the group consisting of anti-CD19, anti-41BBL, anti-OX40L, anti-CD2, anti-CD335, anti-CD16, anti-CD56, anti-CD20, anti-CD80, anti-CD86, anti-CD69, anti-CD154, anti-CD137, and any combination thereof.
56 . The particle of claim 42 , wherein the one or more immunostimulatory or co-stimulatory biomolecules comprise:
an anti-CD3 antibody or an antigen-binding fragment thereof; and/or
an anti-CD28 antibody or an antigen-binding fragment thereof.
57 . The particle of claim 42 , wherein the plurality of macropores comprise between about 2% and about 30% of a total number of pores of the particle, the total number of pores of the particle being a combination of the plurality of micropores and the plurality of macropores.
58 . The particle of claim 42 , wherein the particle comprises the plurality of macropores at a concentration of at least about 2.25% v/v.
59 . The particle of claim 42 , wherein the particle has a diameter between about 1 μm and about 25 μm.
60 . The particle of claim 59 , wherein the particle has a diameter between about 2 μm and about 5 μm.
61 . A particle for inducing an immune cell response, the particle comprising:
a matrix comprising a polymerized monomer having a plurality of micropores and a plurality of macropores; and
one or more immunostimulatory or co-stimulatory biomolecules,
wherein the particle is capable of inducing the immune cell response when contacted with an immune cell, wherein the immune cell response comprises activation and/or expansion of the immune cell, and wherein the particle has a diameter of between about 1 μm and about 25 μm.
62 . The particle of claim 61 , wherein an average diameter of the plurality of micropores is between about 1 nm and about 20 nm.
63 . The particle of claim 61 , wherein the average diameter of the plurality of micropores is between about 2 nm and about 4 nm.
64 . The particle of claim 61 , wherein the immune cell response from contacting the immune cell with the particle is higher than the immune cell response from a control immune cell contacted with an otherwise identical particle lacking the plurality of macropores, and wherein the immune cell response is determined by IL-2 secretion, CD25 expression, or CD69 expression, from the immune cell.
65 . The particle of claim 61 , wherein the immune cell is a T cell.
66 . The particle of claim 61 , wherein the immune cell is a cytotoxic T cell.
67 . The particle of claim 61 , wherein the immune cell is a chimeric antigen receptor (CAR) T cell.
68 . The particle of claim 61 , wherein the particle has a porosity of about 5% to about 95% of a volume of the particle.
69 . The particle of claim 61 , wherein the one or more immunostimulatory or co-stimulatory biomolecules are attached to a surface of the matrix via a linker.
70 . The particle of claim 69 , wherein the linker comprises streptavidin.
71 . The particle of claim 61 , wherein the one or more immunostimulatory or co-stimulatory biomolecules are biotinylated.
72 . The particle of claim 61 , wherein the matrix comprises a bifunctional monomer and wherein the one or more immunostimulatory or co-stimulatory biomolecules are attached to the bifunctional monomer.
73 . The particle of claim 61 , wherein the one or more immunostimulatory or co-stimulatory biomolecules are selected from the group consisting of an anti-CD3 antibody or antigen-binding fragment thereof, an anti-CD28 antibody or antigen-binding fragment thereof, an anti-CD19 antibody or antigen-binding fragment, an anti-41BBL antibody or antigen-binding fragment, an anti-OX40L antibody or antigen-binding fragment, an anti-CD2 antibody or antigen-binding fragment, an anti-CD335 antibody or antigen-binding fragment, an anti-CD16 antibody or antigen-binding fragment, an anti-CD56 antibody or antigen-binding fragment, an anti-CD20 antibody or antigen-binding fragment, an anti-CD80 antibody or antigen-binding fragment, an anti-CD86 antibody or antigen-binding fragment, an anti-CD69 antibody or antigen-binding fragment, an anti-CD154 antibody or antigen-binding fragment, an anti-CD137 antibody or antigen-binding fragment, an IgM antibody or antigen-binding fragment, an IgG antibody or antigen-binding fragment, an IgE antibody or antigen-binding fragment, an IgA antibody or antigen-binding fragment, an IgD antibody or antigen-binding fragment, a toll-like receptor, and any combination thereof.
74 . The particle of claim 61 , wherein the one or more immunostimulatory or co-stimulatory biomolecules are selected from the group consisting of anti-CD19, anti-41BBL, anti-OX40L, anti-CD2, anti-CD335, anti-CD16, anti-CD56, anti-CD20, anti-CD80, anti-CD86, anti-CD69, anti-CD154, anti-CD137, and any combination thereof.
75 . The particle of claim 61 , wherein the one or more immunostimulatory or co-stimulatory biomolecules comprise:
an anti-CD3 antibody or an antigen-binding fragment thereof; and/or
an anti-CD28 antibody or an antigen-binding fragment thereof.
76 . The particle of claim 61 , wherein the plurality of macropores comprise between about 2% and about 30% of a total number of pores of the particle, the total number of pores of the particle being a combination of the plurality of micropores and the plurality of macropores.
77 . The particle of claim 61 , wherein the particle comprises the plurality of macropores at a concentration of at least 2.25% v/v, at least 3.4% v/v, and/or at least 4.5% v/v.
78 . The particle of claim 61 , wherein the particle has a diameter of between about 2 μm and about 5 μm.