Synthetic potency cell mimics for cell therapy quality assessment

Abstract

A synthetic particle including a polymer matrix, at least one antigen, and at least one immune co-stimulatory or adhesion biomolecule is presented. The at least one antigen includes an extracellular domain (ECD) of a protein recognized by an engineered immune receptor, wherein the ECD is configured to induce an antigen-dependent functional response from a plurality of immune effector cells expressing the engineered immune receptor. Related population of synthetic particles method of measuring potency is also presented.

Description

Docket No. SLIN-032 / 01WO 217N-432617-WOSYNTHETIC POTENCY CELL MIMICS FOR CELL THERAPY QUALITY ASSESSMENTCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U. S. Provisional Application No. 63 / 743,334, filed January 92025 and entitled “Immune Induction Hydrogel Beads. " the entire contents of which are incorporated by reference herein.INCORPORATION BY REFERENCE OF SEQUENCE LISTING

[0002] The material in the accompanying sequence listing is hereby incorporated by reference into the application. The accompanying sequence listing XML file, named “SLIN 032 OOUS SeqList ST26.xml”, was created on January 9, 2025 and is 64,719 bytes in size.BACKGROUND

[0003] Immunotherapy involving redirecting specificity of immune cells, including T lymphocytes (T cells), by introducing an engineered immune receptor specific for a cell surface protein is a promising treatment for cancer and autoimmune diseases. Current standards for potency evaluation of engineered immune cells, however, use live cells whose properties vary over storage time, cellular conditions, and even cell passages, resulting in poor consistency between expenmental batches. Tire production of such live cells is also inefficient and carries the risk of contamination. There is a need for improved compositions and methods for evaluating immune cell potency.SUMMARY

[0004] Aspects of the present disclosure relate to a synthetic particle including a polymer matrix, at least one antigen, and at least one immune co-stimulatory or adhesion biomolecule. The at least one antigen includes an extracellular domain (ECD) of a protein recognized by an engineered immune receptor, wherein the ECD is configured to induce an antigen-dependent functional response from a plurality of immune effector cells expressing the engineered immune receptor.

[0005] Aspects of the present disclosure relate to a population of synthetic particles including at least one antigen and at least one immune co-stimulatory or adhesion biomolecule. The at least one antigen includes an extracellular domain (ECD) of a protein recognized by an 1312764302Docket No. SLIN-032 / 01WO 217N-432617-WOengineered immune receptor, wherein the ECD is configured to induce an antigen-dependent functional response from a plurality of immune effector cells expressing the engineered immune receptor. Further, each synthetic particle of the population of synthetic particles includes a polymer matrix.

[0006] Aspects of the present disclosure relate to a method of evaluating potency of immune effector cells, the method includes contacting the immune effector cells with the synthetic particle or population of synthetic particles as described herein.BRIEF DESCRIPTION OF THE FIGURES

[0007] FIG. 1 is a histogram plot showing Interferon-gamma ( IFNy) release upon co-culture of the indicated hydrogel beads with BCMA CAR-T cells. Error bars illustrate the standard deviations of duplicate samples.

[0008] FIG. 2 is a histogram plot showing IFNy release upon co-culture of the indicated hydrogel beads with CD 19 CAR-T cells. Error bars illustrate the standard deviations of duplicate samples.

[0009] FIG. 3 is a histogram plot showing IFNy release upon co-culture of the indicated hydrogel beads with BCMA CAR-T cells at different time intervals. Error bars illustrate the standard deviations of duplicate samples.

[0010] FIG. 4 is a histogram plot showing Interleukin-2 (IL-2) release upon co-culture of tire indicated hydrogel beads with BCMA CAR-T cells at different time intervals. Error bars illustrate the standard deviations of duplicate samples.

[0011] FIG. 5 is a histogram plot showing IFNy release upon co-culture of the indicated hydrogel beads with BCMA CAR-T cells after 18 hours. Error bars illustrate the standard deviations of duplicate samples.

[0012] FIG. 6 is a histogram plot showing IFNy release upon co-culture of the indicated hydrogel beads with CD 19 CAR-T cells and donor-matched untransduced T cells after 6 hours. Error bars illustrate the standard deviations of duplicate samples.

[0013] FIG. 7 is a histogram plot showing IFNy release upon co-culture of the indicated hydrogel beads with CD 19 CAR-T cells and donor-matched untransduced T cells after 18 hours. Error bars illustrate the standard deviations of duplicate samples.

[0014] FIG. 8 is a histogram plot showing IFNy release upon co-culture of the indicated hydrogel beads with CD20 CAR-T cells after 24 hours. Error bars illustrate the standard deviations of duplicate samples.Docket No. SLIN-032 / 01WO 217N-432617-WODETAILED DESCRIPTIONDefinitions

[0015] The indefinite articles “a” and “an” and the definite article “the” are intended to include both the singular and the plural, unless the context in which they are used clearly indicates otherwise.

[0016] “At least one” and “one or more” are used interchangeably to mean that the article may include one or more than one of the listed elements.

[0017] Unless otherwise indicated, it is to be understood that all numbers expressing quantities, ratios, and numerical properties of ingredients, reaction conditions, and so forth, used in the specification are contemplated to be able to be modified in all instances by the term “about”.

[0018] Unless otherwise indicated, it is to be understood that all numbers expressing quantities, ratios, and numerical properties of ingredients, reaction conditions, and so forth, used in the specification are contemplated to be able to be modified in all instances by the term “including all ranges and subranges therebetween”.

[0019] Throughout this application, the term “about” is used to indicate that a value includes the inherent variation of error for the device or the method being employed to determine the value, or the variation that exists among the samples being measured. Unless otherwise stated or otherwise evident from the context, the term “about” means within 10% above or below the reported numerical value (except where such number would exceed 100% of a possible value or go below 0%), When used in conjunction with a range or series of values, the term “about” applies to the endpoints of the range or each of the values enumerated in the series, unless otherwise indicated. As used in this application, the terms “about” and “approximately” are used as equivalents.

[0020] The term “including all ranges and subranges therebetween” or equivalents, are used herein to denote the intention that disclosure of any range or series of possible values, inherently also discloses all ranges and subranges encompassed by the highest and lowest values disclosed. This term includes the entire range from highest to lowest disclosed values, as well as subranges from any two or more disclosed points. This term is also intended to disclose any subranges encompassed anywhere within the highest and lowest disclosed values, including between two points that are explicitly recited in the document, up to one decimal point. Thus, disclosure of values 0, 5, 10, 15, 20, including all ranges and subranges therebetween, should be interpreted as also encompassing a range from 0-20, a range from 0-5 or 5-15, as well as a range from 2-16, or 3.1 to 19.8, etc.Docket No. SLIN-032 / 01WO 217N-432617-WO

[0021] The term “substantially similar,” as may be used herein, when used in reference to a property denotes at least 40% similar, at least 50% similar, at least 60% similar, at least 70% similar, at least 80% similar, at least 90% similar, at least 95% similar, at least 96% similar, at least 97% similar, at least 98% similar, or at least 99% similar to the property. For example, a particle having forward scatter property that is substantially similar to that of an target cell denotes that the forward scatter of the particle is at least 40% similar, at least 50% similar, at least 60% similar, at least 70% similar, at least 80% similar, at least 90% similar, at least 95% similar, at least 96% similar, at least 97% similar, at least 98% similar, or at least 99% similar to the forward scatter of the target cell.

[0022] As maybe used herein, the term “contacting” (i.e., contacting a cell e.g,, a differentiable cell, with a compound or particle) is intended to include (but is not limited to) incubating the compound or particle and the cell together in vitro (e.g., adding the compound / particles to cells in culture). It is understood that the cells contacted with the defined medium can be further treated with a cell differentiation environment to stabilize the cells, or to differentiate the cells.

[0023] As may be used herein, the term “stabilize,” when used in reference to the differentiation state of a cell or culture of cells, indicates that the cells will continue to proliferate over multiple passages in culture, and preferably indefinitely in culture, where most, if not all, of the cells in the culture are of the same differentiation state. In addition, when the stabilized cells divide, the division typically yields cells of the same cell type or yields cells of the same differentiation state. A stabilized cell or cell population in general, does not further differentiate or de-differentiate if the cell culture conditions are not altered and the cells continue to be passaged and are not overgrown. In some embodiments, the cell that is stabilized is capable of proliferation in the stable state indefinitely, or for at least more than 2 passages. In a more specific embodiment, the cells are stable for more than 3 passages, more than 4 passages, more than 5 passages, more than 6 passages, more than 7 passages, more than 8 passages, more than 9 passages, more than 10 passages, more than 15 passages, more than 20 passages, more than 25 passages, or more than 30 passages. In some embodiments, the cell is stable for greater than approximately 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, or 11 months of continuous passaging. In some embodiments, the cell is stable for greater than approximately 1 year of continuous passaging. In some embodiments, stem cells are maintained in culture in a pluripotent state by¬ routine passage in the defined medium until it is desired that they be differentiated. As used herein, the term “proliferate” refers to an increase in the number cells in a cell culture.Docket No. SLIN-032 / 01WO 217N-432617-WO

[0024] Hence, as may be used herein, the term “growth environment” is an environment in which cells will proliferate in vitro. Features of the environment include the medium in w’hich the cells are cultured, and a supporting structure (such as a substrate on a solid surface) if present.

[0025] As may be used herein, a “defined medium” refers to a biochemically defined formulation comprised solely of the biochemically defined constituents, A defined medium may include solely constituents having known chemical compositions. A defined medium may also include constituents that are derived from known sources. For example, a defined medium may also include factors and other compositions secreted from known tissues or cells; however, the defined medium will not include the conditioned medium from a culture of such cells, Tirus, a “defined medium” may, if indicated, include particular compounds added to form the culture medium.

[0026] As may be used herein, the term “basal medium” refers to a solution of ammo acids, vitamins, salts, and nutrients that is effective to support the growth of cells in culture, although normally these compounds will not support cell growth unless supplemented with additional compounds. The nutrients include a carbon source (e.g., a sugar such as glucose) that can be metabolized by the cells, as well as other compounds necessary’ for the cells' survival. These are compounds that the cells themselves cannot synthesize, due to the absence of one or more of the gene(s) that encode the protein(s) necessary to synthesize the compound (e.g., essential amino acids) or, w ith respect to compounds which the cells can synthesize, because of their particular developmental state the gene(s) encoding the necessary biosynthetic proteins are not being expressed as sufficient levels. A number of base media are known in the art of mammalian cell culture, such as Dulbecco's Modified Eagle Media (DMEM), Knockout-DMEM (KO-DMEM), and DMEM / F12, although any base medium that supports the growth of primate embryonic stem cells in a substantially undifferentiated state can be employed. A “basal medium” as described herein also refers to the basal medium described in PCT / US2007 / 062755, filed Jun. 13, 2007, which is herein incorporated by reference in its entirety.

[0027] The term “antigen-binding fragment” refers to a polypeptide fragment that contains at least one complementarity-determining region (CDR) of an immunoglobulin heavy and / or light chain that binds to at least one epitope of the antigen of interest. Antigen-binding fragments include proteins that comprise a portion of a full-length antibody, generally the antigen binding or variable region thereof, such as Fab, F(ab’)2, Fab’, Fv fragments, minibodies, diabodies,Docket No. SLIN-032 / 01WO 217N-432617-WOsingle domain antibody (dAb), single-chain variable fragments (scFv), and multispecific antibodies formed from antibody fragments.

[0028] Tire term “percent identity” in the context of two or more nucleic acid or polypeptide sequences, refers to two or more sequences or subsequences that have a specified percentage of nucleotides or amino acid residues that are the same, when compared. Unless otherwise indicated, percent identity is determined using the National Center for Biotechnology Information (NCBI)’s Basic Local Alignment Search Tool (BLAST®), available at blast.ncbi.nlm.nih.gov / Blast.cgi, version BLAST+ 2.13.0.Overview

[0029] In some embodiments, the disclosure provides a synthetic particle (also referred to herein as “particle” for brevity) including a polymer matrix and at least one antigen. The at least one antigen includes an extracellular domain (ECD) of a protein recognized by an engineered immune receptor, wherein the ECD is configured to induce an antigen-dependent functional response from a plurality of immune effector cells expressing the engineered immune receptor. In some embodiments, the ECD is configured in a substantially native-like configuration to induce the antigen -dependent functional response. In some embodiments, the at least one antigen includes a full-length protein including the ECD, wherein the full-length protein is configured in a substantially native-like configuration to induce the antigendependent functional response. Non-limiting examples of the plurality of immune effector cells expressing the engineered immune receptor include CAR-T cells, CAR-NK cells, CAR-macrophage cells, or combinations thereof. Non-limiting examples of the at least one antigen includes CD19, CD20, or B-cell maturation antigen (BCMA).

[0030] In some embodiments, the synthetic particle further includes at least one immune costimulatory or adhesion biomolecule. In some embodiments, the at least one immune co¬ stimulatory or adhesion biomolecule is selected from the group consisting of: Intercellular Adhesion Molecule 1 (ICAM-1) or a functional fragment thereof, a biomolecule that activates the signaling of CD28, a biomolecule that activates the signaling of CD27, a biomolecule that activates the signaling of CD40, and any combinations thereof. In some embodiments, the biomolecule that activates the signaling of CD28 includes (i) CD80 or a functional fragment thereof and / or (ii) CD86 or a functional fragment thereof; the biomolecule that activates the signaling of CD27 comprises CD70 or a functional fragment thereof; or (c) the biomolecule that activates the signaling of CD40 includes CD40L or a functional fragment thereof, in some embodiments, the immune co-stimulatory or adhesion biomolecule includes ICAM- 1 or theDocket No. SLIN-032 / 01WO 217N-432617-WOfunctional fragment thereof, CD80 or a functional fragment thereof, CD86 or a functional fragment thereof, CD70 or a functional fragment thereof, CD40L or a functional fragment thereof, or any combination thereof. In some embodiments, the synthetic particle is configured to determine functional potency of the plurality of immune effector cells expressing the engineered immune receptor.

[0031] In some embodiments, the disclosure provides compositions and methods for evaluating functional potency of immune effector cells. In some embodiments, the disclosure provides synthetic particles that can engage and act as synthetic cell targets (e.g., functional synthetic cell mimics) for immune effector cells (e.g., CAR-T cells) to measure their potency. In some embodiments, a population of the synthetic particles includes the antigen for the engineered immune receptor. In some embodiments, such a population of the synthetic particles may outperform live biological cells for engaging and functioning as targets for immune effector cells.

[0032] In some embodiments, the population of synthetic particles further includes at least one immune co-stimulatory or adhesion biomolecule, and optionally one or more additional immune co-stimulatory biomolecules. In some embodiments, such a population of the synthetic particles may more effectively engage and act as targets for immune effector cells than a control population of synthetic particles that do not include the at least one immune co- stimulatory or adhesion biomolecule. In some embodiments, the immune effector cells are CAR-T cells and employing the synthetic particles according to embodiments of the present disclosure as synthetic potency targets may lead to enhanced secretion of one or both of IFN-gamma (IFNy) and Interleukin-2 (IL-2).

[0033] Tlie present disclosure is based in part on the unexpected discovery that one or more properties of a synthetic particle can be independently modulated by altering the composition of the particle, for example, by altering the amount of initial monomer (or co-monomer) in the composition, by altering the surface functionalization, by altering the amount of a polymerization initiator or by altering the amount of crosslinker. Furthermore, properties of particles can be tuned without having a substantial effect on density of the particle. This is a surprising and useful feature, as in some embodiments, particles that serve as surrogates for cells benefit from a minimal density in order to function appropriately.

[0034] In embodiments, a method for producing a particle is provided, wherein the particle has one or more properties substantially similar to the properties of one or more target cellsDocket No. SLIN-032 / 01WO 217N-432617-WOemployed for measuring the potency of immune effector cells. In some embodiments, the synthetic particle has pre-determined properties.Synthetic Particles comprising Antigen(s

[0035] In some embodiments, the synthetic particle includes at least one antigen including an extracellular domain (ECD) of a protein recognized by an engineered immune receptor. According to embodiments of the present disclosure, the ECD is configured to induce an antigen-dependent functional response from a plurality of immune effector cells expressing the engineered immune receptor.

[0036] As used herein, the term "‘immune effector cells” refers to immune cells capable of executing a functional biological response upon engagement of an antigen by a receptor expressed on the immune effector cell. Such functional responses may include, but are not limited to, cytokine secretion, cytotoxic activity, degranulation, proliferation, activation marker expression, or combinations thereof.

[0037] Immune effector cells may be naturally occurring immune cells, genetically modified immune cells, or immune cells engineered to express non-native or recombinant receptors, including engineered immune receptors. Immune effector cells may be derived from autologous, allogeneic, or third-party sources and may be primary cells or cell lines. Non¬ limiting examples of immune effector cells include T lymphocytes, natural killer (NK) cells, natural killer T (NKT) cells, gamma delta (yd) T cells, macrophages, monocytes, dendritic cells, and genetically engineered variants thereof.

[0038] In some embodiments, immune effector cells include T cells or NK cells engineered to express a chimeric antigen receptor (CAR), a recombinant antigen receptor, a synthetic immune receptor, or another engineered receptor capable of recognizing an extracellular portion of a target antigen in an MHC-independent manner. In certain embodiments, immune effector cells do not require antigen processing or presentation via major histocompatibility complex (MHC) molecules to elicit a functional response.

[0039] As used herein, the term “engineered immune receptor” refers to a receptor that is introduced into, modified within, or recombinantly expressed by an immune effector cell through human intervention, and that is capable of specifically recognizing a target antigen and inducing a functional response in the immune effector cell upon antigen engagement. An engineered immune receptor may be non-native, synthetic, recombinant, or structurally modified relative to receptors naturally expressed by the immune effector cell. Engineered immune receptors may be designed to recognize at least an extracellular portion of a targetDocket No. SLIN-032 / 01WO 217N-432617-WOantigen in an MHC-independent manner, and may include one or more antigen-binding domains operably linked to one or more intracellular signalling domains.

[0040] Non-limiting examples of engineered immune receptors include chimeric antigen receptors (CARs), recombinant antigen receptors, synthetic immune receptors, antibody- derived receptors, nano body-based receptors, switch receptors, logic-gated receptors, dual¬ specific receptors, and other engineered receptors capable of conferring antigen-dependent functional activity to an immune effector cell.

[0041] In some embodiments, engineered immune receptors include an extracellular antigenbinding domain derived from an antibody or antibody fragment and one or more intracellular signalling domains selected to promote immune effector cell activation, cytotoxicity, cytokine secretion, or other functional responses. Engineered immune receptors are distinguished from native immune receptors, such as endogenous T cell receptors (TCRs) and B cell receptors (BCRs), which arise through physiological immune development and typically recognize antigens in an MHC-restricted or naturally occurring context.

[0042] Non-limiting examples of immune effector cells expressing the engineered immune receptor according to embodiments of the present disclosure include CAR-T cells, CAR-NK cells, CAR-macrophage cells, or combinations thereof.

[0043] As used herein, the term “antigen-dependent functional response” refers to a measurable biological activity of an immune effector cell that is indicative of the functional potency of the immune effector cell, and that occurs specifically as a result of engagement of an engineered immune receptor with its cognate antigen.

[0044] An antigen-dependent functional response is dependent on the presence and configuration of the antigen and is substantially reduced or absent in tire absence of antigen engagement, thereby enabling discrimination of functional activity atributable to the engineered immune receptor. Such responses are suitable for use in potency assays, comparability assessments, lot release testing, or functional characterization of engineered immune effector cell products.

[0045] Non-limiting examples of antigen-dependent functional responses indicative of functional potency include cytotoxic activity, target cell killing, cytokine secretion, degranulation, activation marker expression, or combinations thereof, provided that such responses correlate with antigen-specific activation mediated by the engineered immune receptor. In some embodiments, the antigen dependent functional response is determined by¬Docket No. SLIN-032 / 01WO 217N-432617-WOone or both of interferon-gamma (IFNy) secretion and Interleukin-2 (IL-2) secretion by the plurality of immune effector cells.

[0046] As used herein, the term ‘"antigen” refers to a molecule that is capable of being specifically recognized by an engineered immune receptor expressed by an immune effector cell and of inducing an antigen-dependent functional response indicative of functional potency. In some embodiments, the antigen includes an extracellular domain (ECD) of a protein, wherein the extracellular domain includes one or more epitopes recognized by the engineered immune receptor. Tire extracellular domain may be presented as an isolated extracellular domain, a fragment thereof that retains receptor recognition, or as part of a larger construct, provided that the extracellular domain is accessible for receptor engagement. In some embodiments, the extracellular domain of the antigen is presented in a specific configuration, including a substantially native-like configuration, that preserves structural, conformational, and / or spatial features required for functional engagement by the engineered immune receptor.

[0047] In certain embodiments, the antigen includes a full-length protein that includes the extracellular domain, and optionally further includes a transmembrane domain and / or an intracellular domain. In such embodiments, the full-length protein is configured such that the extracellular domain is presented in a configuration that permits recognition by the engineered immune receptor. In some embodiments, the full length protein is presented in a specific configuration, including a substantially native-like configuration, that preserves structural, conformational, and / or spatial features required for functional engagement by the engineered immune receptor. Such configurations may be achieved, for example, by proper folding, stabilization, anchoring to a matrix or surface, maintenance of physiologically relevant orientation, preservation of post-translational modifications, or combinations thereof. In certain embodiments, the specific or native-like configuration of the extracellular domain or the fill length protein enables the extracellular domain to induce an antigen-dependent functional response from immune effector cells expressing tire engineered immune receptor, thereby serving as a readout of functional potency.

[0048] Non-limiting examples of antigens suitable for use include CD 19, CD20, and B-cell maturation antigen (BCMA). In some embodiments, the at least one antigen includes the extracellular domain of CD 19, CD20, or BCMA. In some embodiments, the at least one antigen includes a full-length CD 19, CD20, or BCMA protein, wherein tire extracellular domain or the full-length protein is presented in a substantially native-like configuration capable of inducingDocket No. SLIN-032 / 01WO 217N-432617-WOan antigen-dependent functional response from immune effector cells expressing an engineered immune receptor.

[0049] The antigens described herein may be derived from natural sources, recombinantly produced, or engineered to enhance stability, presentation, or functional activity, provided that the extracellular domain retains the ability to be recognized by the engineered immune receptor.Synthetic Particles Comprising Immune Co-Stimulatory or Adhesion Biomolecule(s)

[0050] In some embodiments, the disclosure provides a synthetic particle further comprising one or more biomolecules. In some embodiments, the synthetic particle can present the biomolecules to cells, such as immune effector cells. In some embodiments, the synthetic particle comprises at least one immune co-stimulatory or adhesion biomolecule.

[0051] In some embodiments, the at least one co-stimulatory’ or adhesion biomolecule may be atached to the particle via a free amine, free carboxyl / or a free hydroxyl group present on the surface of the particle. F unctionalization of a particle with a biomolecule can also occur through a linker, such as by a streptavidin / biotin conjugate, a biotin / streptavidin conjugate, a streptavidin / biotin / streptavidin conjugate, and / or a biotin / streptavidin / biotin conjugate. For instance, when the particle comprises acrylamide, a streptavidin-biotin linkage can be exploited to attach particular biomolecules to the surface of the particles. Other known binding / linkage methods can be used without departing from the spirit of the present disclosure. In some embodiments, the linker comprises a polypeptide, a ligand, or an antibody

[0052] In some embodiments, the at least one immune co-stimulatory or adhesion biomolecule is selected from the group consisting of: Intercellular adhesion molecule 1 (ICAM-1) or a functional fragment thereof, a biomolecule that activates the signaling of CD28, a biomolecule that activates the signaling of CD40, a biomolecule that activates the signaling of CD27, and any combination thereof.

[0053] In some embodiments, the at least one immune co-stimulatory or adhesion biomolecule further comprises at least a biomolecule selected from the group consisting of a biomolecule that activates the signaling of CD3, a biomolecule that activates the signaling of ICOS (CD278), a biomolecule that activates the signaling of 0X40 (CD 134), a biomolecule that activates the signaling of 4-1BB (CD137), a biomolecule that activates the signaling of Tolllike receptor (TLR), a biomolecule that activates the signaling of HVEM (TNFSFR14 or CD270), a biomolecule that activates the signaling of LIGHT (TNFSF14, CD258), a biomolecule that activates the signaling of DR3 (TNFRSF25), a biomolecule that activates theDocket No. SLIN-032 / 01WO 217N-432617-WOsignaling of GITR (CD357), a biomolecule that activates the signaling of CD30 (TNFRSF8), a biomolecule that activates the signaling of TIM1 (HAVCR1, KIMI), a biomolecule that activates the signaling of SLAM (CD 150, SLAMF1), a biomolecule that activates the signaling of CD226 (DNAM1), and any combination thereof. In some embodiments, the at least one immune co-stimulatory or adhesion biomolecule is selected from one or more immune co-stimulatory or adhesion biomolecules listed in Table 1, and any combination thereof. In some embodiments, the at least one immune co-stimulatory or adhesion biomolecule or functional fragment thereof comprises an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to any of the immune co-stimulatory’ or adhesion biomolecule sequences of Table 1, or the extracellular portion thereof, including all ranges and subranges therebetween.

[0054] In some embodiments, the particle of the disclosure comprises a combination of at least two, at least three, at least four, or at least five of the immune co-stimulatory or adhesion biomolecules. In some embodiments, a population of the particles of the disclosure comprise a combination of at least two, at least three, at least four, or at least five of the immune co-stimulatory or adhesion biomolecules.

[0055] Additional descriptions of immune co-stimulatory or adhesion biomolecules can be found, for example, in Chen and Flies, Nat Rev Immunol. 2013 Apr., 13(4):227-42; and Weinkove et al., Clin Transl Immunology, 2019 May II, 8(5):el049, the content of each of which is incorporated by reference herein in its entirety for all purposes.Table 1. Non-limiting Examples of Immune Co-Stimulatory or Adhesion Biomolecules and Corresponding Immune Response BiomoleculesNon-limiting Examples of Immune Co-Stimulatory Immune Response Biomolecules or Adhesion BiomoleculesICAM-1 (Uniprot ID: P05362; SEQ ID NO: 43) or Lymphocyte function-associated functional fragment thereof antigen 1 (LFA-1), which is a complex of CD Ila (Uniprot ID: P20701; SEQ ID NO: 50) and CD 18 (Uniprot ID: P05107; SEQ ID NO: 52).Docket No. SLIN-032 / 01WO 217N-432617-WONon-limiting Examples of Immune Co-Stimulatory Immune Response Biomolecules or Adhesion BiomoleculesMacrophage antigen 1 (Mac-1), which is a complex of CD1 lb (Uniprot ID: Pl 1215; SEQ ID NO: 54) and CD 18 (Uniprot ID:P05107; SEQ ID NO: 52).CDS agonist (e.g., anti-CD3 antibody or antigen CD3 (formed by at least one of: binding fragment thereof) CD3 gamma (Uniprot ID: P09693;SEQ ID NO: 16); CD3 delta (Uniprot ID: P04234; SEQ ID NO: 17); CD3 epsilon (Uniprot ID: P07766; SEQ ID NO: 18); and / or CD3 zeta (Uniprot ID: P20963; SEQ ID NO: 19))CD80 (Uniprot ID: P3368I; SEQ ID NO: 6) or CD28 (Uniprot ID: P10747; SEQ functional fragment thereof; CD86 (Uniprot ID: ID NO: 5)P42081; SEQ ID NO: 7) or functional fragmentthereof; anti-CD28 antibody or antigen bindingfragment thereofICOS-L (CD275) (Uniprot ID: 075144) or functional ICOS (CD278) (Uniprot ID: fragment thereof (e.g., comprising SEQ ID NO: 13); Q9Y6W8; SEQ ID NO: 12) anti-ICOS antibody or antigen binding fragmentthereof.CD70 (Uniprot ID: P32970) or functional fragment CD27 (TNFRSF7) (Uniprot ID: thereof (e.g., comprising SEQ ID NO: 15); anti-CD27 P26842; SEQ ID NO: 14) antibody or antigen binding fragment thereof.CD40L (CD 154) (Uniprot ID: P29965) or functional CD40 (Uniprot ID: P25942; SEQ fragment thereof (e.g., comprising SEQ ID NO: 11 or ID NO: 8)41); anti-CD40 antibody or antigen binding fragmentthereof.Docket No. SLIN-032 / 01WO 217N-432617-WONon-limiting Examples of Immune Co-Stimulatory Immune Response Biomolecules or Adhesion BiomoleculesCD40 (Uniprot ID: P25942) or functional fragment CD40L (Uniprot ID: P29965; SEQ thereof (e.g., comprising SEQ ID NO: 9); anti-CD40L ID NO: 10)antibody or antigen binding fragment thereof.OX40L (Uniprot ID: P23510; SEQ ID NO: 2) or 0X40 (CD134) (Uniprot ID: functional fragment thereof; anti-OX40 antibody or P43489; SEQ ID NO: 4) antigen binding fragment thereof4-1BBL (Uniprot ID: P41273; SEQ ID NO: 1) or 4- IBB (CD 137) (Uniprot ID: functional fragment thereof; anti-4- IBB antibody or Q07011; SEQ ID NO: 3) antigen binding fragment thereofTLR agonist Toll-like receptor (TLR) (e.g., TLR1 (Uniprot ID: QI 5399); TLR2 (Uniprot ID: 060603); TLR3 (Uniprot ID: 015455); TLR4 (Uniprot ID: 000206); TLR5 (Uniprot ID: 060602); TLR6 (Uniprot ID: Q9Y2C9); TLR7 (Uniprot ID: Q9NYK1); TLR8 (Uniprot ID: Q9NR97); TLR9 (Uniprot ID: Q9NR96); or TLR10 (Uniprot ID: Q9BXR5)) LIGHT (TNFSF14, CD258) (Uniprot ID: 043557) or HVEM (TNFSFR14 or CD270) functional fragment thereof (e.g., comprising SEQ ID (Uniprot ID: Q92956; SEQ ID NO: 21); anti-HVEM antibody or antigen binding NO: 20)fragment thereofHVEM (TNFSFR14 or CD270) (Uniprot ID: Q92956) LIGHT (TNFSF14, CD258) or functional fragment thereof (e.g., comprising SEQ (Uniprot ID: 043557; SEQ ID ID NO: 23); anti-LIGHT antibody or antigen binding NO: 22)fragment thereofTL1A (Uniprot ID: 095150) or functional fragment DR3 (TNFRSF25) (Uniprot ID: thereof (e.g., comprising SEQ ID NO: 25); anti-DR3 Q93038; SEQ ID NO: 24) antibody or antigen binding fragment thereofDocket No. SLIN-032 / 01WO 217N-432617-WONon-limiting Examples of Immune Co-Stimulatory Immune Response Biomolecules or Adhesion BiomoleculesGITRL (Uniprot ID: Q9UNG2) or functional fragment GITR (CD357) (Uniprot ID: thereof (e.g., comprising SEQ ID NO: 27); anti-GITR Q9Y5U5; SEQ ID NO: 26) antibody or antigen binding fragment thereofCD30L (Uniprot ID: P32971) or functional fragment CD30 (TNFRSF8) (Uniprot ID: thereof (e.g., comprising SEQ ID NO: 29); anti-CD30 P28908; SEQ ID NO: 28) antibody or antigen binding fragment thereofTIMl ligand or functional fragment thereof; TIM4 or TIM1 (HAVCR1, KIMI) (Uniprot functional fragment thereof; anti-TIMl antibody or ID: Q96D42; SEQ ID NO: 30) antigen binding fragment thereofSLAM (Uniprot ID: QI 3291) or functional fragment SLAM (CD 150, SLAMF1) thereof (e.g., comprising SEQ ID NO: 32); anti-SLAM (Uniprot ID: Q13291; SEQ ID antibody or antigen binding fragment thereof NO: 31)CD48 (Uniprot ID: P09326) or functional fragment CD2 (LFA-2) (Uniprot ID: thereof (e.g., comprising SEQ ID NO: 34); CD58 P06729; SEQ ID NO: 33) (Uniprot ID: P19256) or functional fragment thereof(e.g., comprising SEQ ID NO: 35 or 42); anti-CD2antibody or antigen binding fragment thereofCD 155 (Uniprot ID: P15151) or functional fragment CD226 (DNAM1) (Uniprot ID: thereof (e.g., comprising SEQ ID NO: 37); CD1I2 Q15762; SEQ ID NO: 36) (Uniprot ID: Q92692) or functional fragment thereof(e.g., comprising SEQ ID NO: 38); anti-CD226antibody or antigen binding fragment thereof|0056] In some embodiments, the immune co-stimulatory or adhesion biomolecule binds to the corresponding target biomolecule (e.g., an immune response biomolecule tethered to an immune effector cell) with a dissociation constant (Kd) of less than 10 pM, less than 1 gM, less than 100 nM, less than 10 nM, or less than 1 nM, as measured by surface plasmon resonance (SPR) method using a sensor chip that contains immobilized immune co-stimulatory or adhesion biomolecules.

[0057] In some embodiments, the particle comprises between about 1 and about 100,000,000 copies of the one or more biomolecules (e.g., immune co-stimulatory or adhesionDocket No. SLIN-032 / 01WO 217N-432617-WObiomolecules). In some embodiments, the particle is approximately the same size as the target cell and comprises between about 500 and 100,000,000 copies ofthe one or more biomolecules. In some embodiments, the particle is approximately about 5 pm to about 200 pm and comprises between about 500 and 100,000,000 copies of the one or more biomolecules. In some embodiments, the particle has a diameter of at least 5 pm. In some embodiments, the particle comprises at least the same number of the one or more biomolecules as binding sites of the target cell. In some embodiments, the particle comprises more ofthe one or more biomolecules than the corresponding binding sites of the target cell. In some embodiments, the particle comprises at least 1, at least 10, at least 100, at least 1,000, at least 10,000, at least 100,000, at least 1,000,000, at least 10,000,000, or at least 100,000,000 copies of the one or more biomolecules.

[0058] In some embodiments, the biomolecules are attached to the surface of the synthetic particle. In some embodiments, the biomolecules are in the matrix ofthe synthetic particle itself (e.g., encapsulated or embedded within the particle). In some embodiments, the synthetic particle is engineered to degrade to provide such biomolecule to the immune effector cell. The rate of degradation can be modulated to provide slow degradation of the particle and thus slow release of the biomolecule to the immune effector cell. In some embodiments, the biomolecules are attached to both the surface of the particle and in the matrix of the synthetic particle. In some embodiments, the biomolecules on the surface and in the matrix of the synthetic particle are the same. In some embodiments, the biomolecules on the surface and in the matrix of the synthetic particle are different. In some embodiments, the biomolecules on the surface and in the matrix of the synthetic particle are different and the components of the matrix dissolve at different rates.Exemplary Immune Co-Stimulatory or Adhesion Biomolecules and Immune Response Biomolecules

[0059] In some embodiments, the particle of the disclosure comprises an adhesion biomolecule.

[0060] In some embodiments, the adhesion biomolecule comprises ICAM-1 or the functional fragment thereof. ICAM-1 (Intercellular adhesion molecule 1, also known as CD54) belongs to the Ig superfamily and its canonical form consists of five extracellular Ig domains, a transmembrane domain, and a short cytoplasmic domain. The five Ig domains of ICAM-1 are:Docket No. SLIN-032 / 01WO 217N-432617-WO1) ICAM-1 Ig domain #1: corresponding to amino acids 41-103 of SEQ ID NO: 43. In some embodiments, the ICAM-1 Ig domain #1 comprises an amino acid sequence at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 45;2) ICAM-1 Ig domain #2: corresponding to amino acids 128-193 of SEQ ID NO: 43. In some embodiments, the ICAM-1 Ig domain #2 comprises an amino acid sequence at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 46;3) ICAM-1 Ig domain #3: corresponding to amino acids 230-297 of SEQ ID NO: 43. In some embodiments, the ICAM-1 Ig domain #3 comprises an amino acid sequence at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 47;4) ICAM-1 Ig domain #4: corresponding to amino acids 325-378 of SEQ ID NO: 43. In some embodiments, the ICAM-1 Ig domain #4 comprises an amino acid sequence at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 48;5) ICAM-1 Ig domain #5: corresponding to amino acids 412-464 of SEQ ID NO: 43. In some embodiments, the ICAM-I Ig domain #5 comprises an amino acid sequence at least 80%, 85%, 90%, 95%, 98%, 99%, or 100% identical to SEQ ID NO: 49.These Ig domains mediate ICAM-1 interactions with its ligands. Upon ligation, ICAM-1 undergoes dimerization / multimerization and clustering through homotypic binding between Ig domains 3 and 4, which significantly increases ICAM-1 binding affinity to its cognate ligands?2-integrins lymphocyte function-associated antigen 1 (LFA-1; CDlla / CD18) and macrophage antigen 1 (Mac-1; CDllb / CD18). LFA-1 and Mac-1 are known to bind Ig domains I and 3, respectively. The functions of ICAM-I include regulating leukocyte trafficking and mediating immune cell effector function.

[0061] The canonical form of ICAM-1 in homo sapiens is provided, for example, in Uniprot database under Uniprot ID P05362, with the protein sequence of SEQ ID NO: 43. ICAM-1 is post-transcriptionally regulated by alternative splicing, which generates at least six membrane¬ bound isoforms and the corresponding secretable soluble forms (si CAM- 1). All ICAM-1 isoforms consist of at least Ig domains I and 5, In addition to the canonical form, which comprises all five Ig domains #1 to #5, the other five membrane-bound variants include: a) ICAM-1 isoform “4-6”: composing Ig domains #1, #2, #3, and #5;b) ICAM-1 isoform “2-4”: comprising Ig domains #1, #3, #4, and #5;c) ICAM-1 isoform “3-6”: comprising Ig domains #1, #2, and #5;d) ICAM-1 isoform “2-5”: comprising Ig domains #1, #4, and #5; ande) ICAM-1 isoform “2-6”: comprising Ig domains #1 and #5,Docket No. SLIN-032 / 01WO 217N-432617-WO

[0062] Further descriptions of ICAM-1 can be found, for example, in Bui et al., J Leukoc Biol.2020 Mar. 17, 108(3):787-799 and Robledo et al., Eur J Immunol. 2003 May, 33(5): 1351-60, the contents of each of which are hereby incorporated by reference in their entireties for all purposes.

[0063] In some embodiments, the functional fragment of ICAM-1 comprises the part of its extracellular domain capable of binding to LFA-l and / or Mac-1. In some embodiments, the ICAM-1 or the functional fragment thereof comprises the extracellular portion of the ICAM-1 protein. In some embodiments, the ICAM-1 or the functional fragment thereof comprises an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 44, including all ranges and subranges therebetween. In some embodiments, the extracellular portion of the ICAM-I protein encompasses all five Ig domains. In some embodiments, the ICAM-1 or the functional fragment thereof comprises the extracellular portion of an ICAM-1 isoform. In some embodiments, the ICAM-1 or the functional fragment thereof comprises the specific Ig domains corresponding to those in a specific ICAM-1 isoform:In some embodiments, the ICAM-1 or the functional fragment thereof comprises the specific Ig domains corresponding to those in ICAM-I isoform “4-6” (i.e., Ig domains #1, #2, #3, and #5); in some embodiments, such ICAM-1 comprises four polypeptide segments each having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 45, 46, 47, and 49, respectively, including all ranges and subranges therebetween; In some embodiments, the ICAM-1 or the functional fragment thereof comprises the specific Ig domains corresponding to those in ICAM-1 isoform “2-4” (i.e., Ig domains #1, #3, #4, and #5); in some embodiments, such ICAM-1 comprises four polypeptide segments each having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 45, 47, 48, and 49, respectively, including all ranges and subranges therebetween; In some embodiments, the ICAM-1 or the functional fragment thereof comprises the specific Ig domains corresponding to those in ICAM-1 isoform “3-6” (i.e,, Ig domains #1, #2, and #5); in some embodiments, such ICAM-I comprises three polypeptide segments each having at least 80%. at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 45, 46, and 49, respectively, including all ranges and subranges therebetween;DocketNo. SLIN-032 / 01WO 217N-432617-WOIn some embodiments, the ICAM-l or the functional fragment thereof comprises the specific Ig domains corresponding to those in ICAM-l isoform “2-5” (i.e., Ig domains #1, #4, and #5); in some embodiments, such ICAM-l comprises three polypeptide segments each having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 45, 48, and 49, respectively, including all ranges and subranges therebetween; In some embodiments, the ICAM-l or the functional fragment thereof comprises the specific Ig domains corresponding to those in ICAM-l isoform “2-6” (i.e., Ig domains #1 and #5); in some embodiments, such ICAM-l comprises two polypeptide segments each having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 45 and 49, respectively, including all ranges and subranges therebetween;

[0064] In some embodiments, the particle of the disclosure comprises an immune costimulatory biomolecule that activates CD28 receptor signaling. In some embodiments, the biomolecule that activates CD28 receptor signaling is a CD28 ligand, a ligand mimic, an antibody, a peptide, an aptamer, or a small molecule. In some embodiments, the immune costimulatory biomolecule that activates CD28 receptor signaling binds CD28 receptor with a dissociation constant (Kd) of less than 10 pM, less than 1 pM, less than 100 nM, less than 10 nM, or less than 1 nM, as measured by surface plasmon resonance (SPR) method using a sensor chip that contains immobilized immune co-stimulatory biomolecules. In some embodiments, the biomolecule that activates CD28 receptor signaling comprises an antibody that specifically binds CD28 receptor, or the antigen-binding fragment thereof. In some embodiments, the biomolecule that activates CD28 receptor signaling is B7-1 (CD80) or B7-2 (CD86), or a functional fragment thereof. Non -limiting examples of immune co-stimulatory’ biomolecules that activate CD28 receptor signaling includes those antibodies, aptamers, ligand proteins disclosed in Pastor et al. Mol Ther Nucleic Acids, (2013) June 11, 2:e98; U. S. Application Publication Nos. 20200268845; 20030232323; 20140271677; 20040137577; 20020106730: and 20100303811; and International Application Publication Nos. W02014089009; WO 1995003408, the contents of each of which are hereby incorporated by reference in their entireties for all purposes.

[0065] In some embodiments, the biomolecule that activates CD28 receptor signaling comprises an anti-CD28 receptor antibody or antigen binding fragment thereof. In some embodiments, the anti-CD28 receptor antibody or antigen binding fragment thereof binds CD28 (e.g., in a domain outside the basolateral domain) and co-stimulates T cells in a TCR-Docket No. SLIN-032 / 01WO 217N-432617-WOdependent mechanism. In some embodiments, the anti-CD28 receptor antibody or antigen binding fragment thereof is a “superagonistic” one that binds CD28 through the basolateral domain resulting in a polyclonal activation of T lymphocytes even in the absence of TCR stimulation. In some embodiments, the superagonistic anti-CD28 antibody is TGN1412 (TAB08). Additional non-limiting examples of anti-CD28 antibodies and antigen binding fragments thereof are disclosed in Poirier et al. (2012) American Journal of Transplantation 12(7): 1682-1690; and Yu-hua Qiu et al, Cell Immunol. 2005 July-August; 236(1-2): 154-60, the contents of each of which are hereby incorporated by reference in their entireties for all purposes. In some embodiments, the anti-CD28 antibody or antigen binding fragment thereof comprises, or is derived form, a mouse IgGl monoclonal antibody (clone CD28.2) available from BioLegend® (e.g., Catalog # 302901 or 302902).

[0066] In some embodiments, the biomolecule that activates CD28 receptor signaling comprises a B7-1 (CD80) ligand or a functional fragment thereof. The canonical form of B7-1 (CD80) in homo sapiens is provided, for example, in Uniprot database under Uniprot ID P33681. In some embodiments, the functional fragment of the B7-1 (CD80) comprises the part of its extracellular domain capable of binding to and activating the CD28 receptor. In some embodiments, the B7-1 (CD80) or the functional fragment thereof comprises an ammo acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 6, including all ranges and subranges therebetween. In some embodiments, the B7-1 (CD80) or the functional fragment thereof comprises the extracellular portion of the B7-1 (CD80) protein. In some embodiments, the B7-1 (CD80) or the functional fragment thereof comprises an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 39, including all ranges and subranges therebetween. SEQ ID NO: 39 encompasses amino acids 35-230 of SEQ ID NO: 6, an extracellular region of the canonical form of CD80 that contains two Ig-like domains.

[0067] In some embodiments, the biomolecule that activates CD28 receptor signaling comprises a B7-2 (CD86) ligand or a functional fragment thereof. The canonical form of B7-2 (CD86) in homo sapiens is provided, for example, in Uniprot database under Uniprot ID P42081. In some embodiments, the functional fragment of the B7-2 (CD86) comprises the part of its extracellular domain capable of binding to and activating the CD28 receptor. In some embodiments, the B7-2 (CD86) or the functional fragment thereof comprises an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 7, including all ranges and subrangesDocket No. SLIN-032 / 01WO 217N-432617-WOtherebetween. In some embodiments, the B7-2 (CD86) or the functional fragment thereof comprises the extracellular portion of the B7-2 (CD86) protein. In some embodiments, the B7-2 (CD86) or the functional fragment thereof comprises an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 40, including all ranges and subranges therebetween. SEQ ID NO: 40 encompasses amino acids 33-225 of SEQ ID NO: 7, an extracellular region of the canonical form of CD86 that contains two Ig-like domains.

[0068] In some embodiments, the particle of the disclosure comprises an immune costimulatory biomolecule that activates CD40 receptor signaling. In some embodiments, the biomolecule that activates CD40 receptor signaling is a CD40 ligand, a ligand mimic, an antibody, a peptide, an aptamer, or a small molecule. The ligand of CD40 is known as CD154 (CD40L). CD40 signaling may utilize adapter proteins called TNF receptor-associated factors, resulting in the activation of both the canonical and noncanonical NFKB pathways, MAP kinase, PI3 kinase, and phospholipase-Cy, leading to transcriptional activation, cytoskeletal rearrangement and cell survival. A canonical form of human CD40 protein is provided, for example, in Uniprot database under Uniprot ID P25942, with the amino acid sequence of SEQ ID NO: 8.

[0069] In some embodiments, the immune co-stimulatory biomolecule that activates CD40 receptor signaling binds CD40 receptor with a dissociation constant (Kd) of less than 10 pM, less than 1 pM, less than 100 nM, less than 10 nM, or less than 1 nM, as measured by surface plasmon resonance (SPR) method using a sensor chip that contains immobilized immune costimulatory biomolecules. In some embodiments, the biomolecule that activates CD40 receptor signaling comprises an antibody that specifically binds CD40 receptor, or the antigen-binding fragment thereof. In some embodiments, the biomolecule that activates CD40 receptor signaling is CD40L, or a functional fragment thereof.

[0070] In some embodiments, the biomolecule that activates CD40 receptor signaling comprises a CD40 ligand (CD40L) or a functional fragment thereof. The canonical form of CD40L (also known as CD 154) in homo sapiens is provided, for example, in Uniprot database under Uniprot ID P29965. CD40L may be expressed as a type II transmembrane protein, or in a soluble form. CD40L is a member of the TNF superfamily and is characterized by a sandwich extracellular structure that allows for its trimerization, a feature of the TNF family of ligands, CD40L is expressed primarily by activated T cells, as well as activated B cells and platelets; and under inflammatory conditions is also induced on monocytic cells, natural killer cells, mast cells, and basophils. In some embodiments, the functional fragment of the CD40L comprisesDocket No. SLIN-032 / 01WO 217N-432617-WOthe part of its extracellular domain capable of binding to and activating the CD40 receptor. In some embodiments, the CD40L or the functional fragment thereof comprises an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%. at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 10, including all ranges and subranges therebetween. In some embodiments, the CD40L or the functional fragment thereof comprises the extracellular portion of the CD40L protein. In some embodiments, the CD40L or the functional fragment thereof comprises an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%. at least 99%, or 100% identical to SEQ ID NO: 11, including all ranges and subranges therebetween. In some embodiments, the CD40L orthe functional fragment thereof comprises an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to SEQ ID NO: 41, including all ranges and subranges therebetween, SEQ ID NO: 41 represents a soluble form of CD40L that has been shown to be biologically active according to Mazzei et al., J Biol Chem. 1995 Mar 31, 270(13):7025-8, the content of which is incorporated by reference in its entirety for all purposes.

[0071] Further descriptions of CD40 / CD40L and their activation can be found, for example, in Elgueta et al., Immunol Rev. 2009 May, 229(1): 152-72; and Bullock, Cell Mol Immunol, 2022 Jan, 19(1): 14-22, the contents of each of which are hereby incorporated by reference in their entireties for all purposes.Optional Components of the Synthetic Particles

[0072] In some embodiments, the particle comprises one or more molecules that support cell growth and / or stimulate target cell proliferation or activation. These molecules include, but are not limited to, cytokines, growth factors, cytokine receptors, extracellular matrix, transcription factors, secreted polypeptides and other molecules, and growth factor receptors, or fragments thereof. In some embodiments, the particle comprises a fibroblast growth factor (bFGF), an acidic fibroblast growth factor (aFGF), an epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-I), insulin-like growth factor-II (IGF-II), a platelet-derived growth factor-AB (PDGF), a vascular endothelial cell growth factor (VEGF), activin-A, a bone morphogenic protein (BMP), a chemokine, a morphogen, a neutralizing antibody, a heregulin, an interferon, a macrophage-derived cytokine, an interleukin, an interleukin receptor, IL-1, IL -2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18, IL- 19, IL-20, IL-21, IL-22, IL-23, IL-24, IL-25, IL-26, IL-28, IL-29, IL-30, IL-31, IL-32, IL-33,Docket No. SLIN-032 / 01WO 217N-432617-WOIL-34, IL-35, IL-36, IL-37, IL-38, tumor necrosis factor, TNFa, TNFβ, TNFR1, TNFR2, IFNAR1, IFNAR2, TGFR1, TGFR2, FGF, granulocyte macrophage colony-stimulating factor, chemokines (e.g. CCL1, CCL2, CCL3, CCL, CCL5, and CXCL8), CD27 ligand (CD27L), CD40L, CD137L, TNF-related apoptosis-inducing ligand (TRAIL), TNF-related activation- induced cytokine (TRANCE), TNF-related weak inducer of apoptosis (TWEAK), B cell activating factor (BAFF), LIGHT (homologous to lymphotoxin, exhibits inducible expression and competes with herpes simplex virus glycoprotein D for binding to herpesvirus entry mediator, a receptor expressed on T lymphocytes), TNF-like cytokine 1A (TL1A), glucocorticoid-induced TNF receptor-related protein ligand (GITRL), transforming growth factor a (TGF-a), TGF-β, vascular endothelial growth factor (VEGF), nerve growth factor (NGF), macrophage colony- stimulating factor (M-CSF), granulocyte-macrophage colony- stimulating factor (GM-CSF), IFN-a, IFN-β, and IFN-y.Population of Synthetic Particles

[0073] In some embodiments, the disclosure provides a population of synthetic particles. The population of synthetic particles includes at least one antigen including an extracellular domain (ECD) of a protein recognized by an engineered immune receptor, wherein the ECD is configured to induce an antigen-dependent functional response from a plurality of immune effector cells expressing the engineered immune receptor. The population of synthetic particles further includes at least one immune co-stimulatory or adhesion biomolecule. Each synthetic particle of the population of synthetic particles includes a polymer matrix.

[0074] In some embodiments, the at least one antigen and the at least one immune costimulatory or adhesion biomolecule are conjugated to different synthetic particles. In some embodiments, the at least one antigen and the at least one immune co-stimulatory or adhesion biomolecule are conjugated to the same synthetic particle. In some embodiments, the population of synthetic particles includes at least two different types of immune co-stimulatory or adhesion biomolecules, which are present on the same particles. In some embodiments, the population of synthetic particles comprise, overall, at least two different types of immune co-stimulatory or adhesion biomolecules, which are present on different subpopulation of synthetic particles. In some embodiments, all or a part of the particles in the population comprise only one of the immune co-stimulatory or adhesion biomolecules, but the population of synthetic particles overall contain the at least two immune co-stimulatory or adhesion biomolecules, which may be achieved by mixing different subpopulations of synthetic particlesDocket No. SLIN-032 / 01WO 217N-432617-WOthat contain different types of biomolecules. In some embodiments, the antigen is co-localized with at least one of the immune co-stimulatory or adhesion biomolecules on the same (sub)population of synthetic particles. In some embodiments, the antigen is present on a different subpopulation of synthetic particles.Method of evaluating Potency of Synthetic Particles

[0075] In some embodiments, the disclosure provides a method of evaluating potency of immune effector cells. The method includes contacting the immune effector cells with the population of synthetic particles as described herein. The method further includes evaluating the antigen dependent functional response from the plurality of immune effector cells.

[0076] As used herein, the term “antigen-dependent functional response” refers to a measurable biological activity of an immune effector cell that is indicative of the functional potency of the immune effector cell, and that occurs specifically as a result of engagement of an engineered immune receptor with its cognate antigen.

[0077] An antigen-dependent functional response is dependent on the presence and configuration of the antigen and is substantially reduced or absent in the absence of antigen engagement, thereby enabling discrimination of functional activity attributable to the engineered immune receptor. Such responses are suitable for use in potency assays, comparability assessments, lot release testing, or functional characterization of engineered immune effector cell products.

[0078] Non-limiting examples of antigen-dependent functional responses indicative of functional potency include cytotoxic activity, target cell killing, cytokine secretion, degranulation, activation marker expression, or combinations thereof, provided that such responses correlate with antigen-specific activation mediated by the engineered immune receptor.

[0079] In some embodiments, the antigen dependent functional response is determined by one or both ofinterferon-gamma (IFNy) secretion and Interleukin-2 (IL-2) secretion by the plurality of immune effector cells. In some embodiments, the antigen dependent functional response is determined by interferon-gamma (IFNy) secretion from the plurality of immune effector cells. In some embodiments, the antigen dependent functional response is determined by Interleukin- 2 (IL-2) secretion from the plurality of immune effector cells.Docket No. SLIN-032 / 01WO 217N-432617-WOSynthetic Particles with Matrix

[0080] In some embodiments, the present disclosure teaches synthetic particles ((also referred to herein as “particles”) with a polymer matrix. Various synthetic particles of the present disclosure are described herein. In embodiments, the particles of the present disclosure comprise hydrogel particles. A hydrogel is a material comprising a macromolecular three-dimensional network that allows it to swell when in tire presence of water, to shrink in the absence of (or by reduction of the amount of) water, but not dissolve in water. The swelling, i.e., the absorption of water, is a consequence of the presence of hydrophilic functional groups attached to or dispersed within the macromolecular network. Crosslinks between adjacent macromolecules result in the aqueous insolubility of these hydrogels. The cross-links may be due to chemical (i.e., covalent) or physical (i.e., Van Der Waal forces, hydrogen-bonding, ionic forces, etc.) bonds. Synthetically prepared hydrogels can be prepared by polymerizing a monomeric material to form a backbone and cross-linking the backbone with a crosslinking agent. As referred to herein, the term “hydrogel” refers to the macromolecular material whether dehydrated or in a hydrated state. A characteristic of a hydrogel that is of particular value is that the material retains the general shape, whether dehydrated or hydrated. Thus, if the hydrogel has an approximately spherical shape in the dehydrated condition, it will be spherical in the hydrated condition. In some embodiments, the particles may be bioreactors, achieved by allowing the porous particles to absorb water, maintain an optimal ion nutrient gradient, and maintain an optimal osmotic pressure which favors cellular growth and cell activation. It is well established in tissue engineering that cell migration is influenced by hydrogel stiffness and rough surface area. Without wishing to be bound by any one theory, the inventors believe that hydrogel particles of tire present disclosure lead to the formation of much stronger cell-ligand bonds, thereby leading to enhanced growth and proliferation.

[0081] In some embodiments, a hydrogel particle disclosed herein comprises greater than about 30%, greater than about 35 %, greater than about 40%, greater than about 45%, greater than about 50%, greater than about 55%, greater than about 60%, greater than about 65%, greater than about 70%, greater than about 75%, greater than about 80%, greater than about 85%, greater than about 90%, or greater than about 95% water by weight. In some embodiments, a hydrogel particle has a water content of about 10 percent by weight to about 95 percent by weight, or about 20 percent by weight to about 95 percent by weight, or about 30 percent by weight to about 95 percent by weight, or about 40 percent by weight to about 95 percent by weight, or about 50 percent by weight to about 95 percent by weight, or about 60Docket No. SLIN-032 / 01WO 217N-432617-WOpercent by weight to about 95 percent by weight, or about 70 percent by weight to about 95 percent by weight, or about 80 percent by weight to about 95 percent by weight.Degradable Particles

[0082] In some embodiments, an individual particle or a plurality thereof comprises a biodegradable polymer. In some embodiments, the biodegradable polymer is a poly(esters) based on polylactide (PLA), polyglycolide (PGA), polycaprolactone (PCL), poly(lactic-co-glycolic) acid (PLGA), and their copolymers. In some embodiments, the biodegradable polymer is a carbohydrate or a protein, or a combination thereof. For example, in some embodiments, a monosaccharide, disaccharide or polysaccharide, (e.g,, glucose, sucrose, or maltodextrin) peptide, protein (or domain thereof) is used as a monomer for the particles. Other biodegradable polymers include poly(hydroxyalkanoate)s of tire PHB-PHV class, additional poly(ester)s, and natural polymers, for example, modified poly(saccharide)s, e.g., starch, cellulose, and chitosan. In some embodiments, the biocompatible polymer is an adhesion protein, cellulose, a carbohydrate, a starch (e.g., maltodextrin, 2-hydroxyethyl starch, alginic acid), a dextran, a lignin, a polyaminoacid, an amino acid, or chitin. Such biodegradable polymers are available commercially, for example, from Sigma Aldrich (St, Louis, MO).

[0083] In some embodiments, the protein comprises only natural amino acids. However, the disclosure is not limited thereto. For example, self-assembling artificial proteins and proteins with non-natural amino acids (e.g., those incorporated into non-ribosomal peptides or synthetically introduced via synthetic approaches, see for example, Zhang et al. (2013), Current Opinion in Structural Biology 23, pp. 581-587, the disclosure of which is incorporated by reference in its entirety for all purposes), or protein domains thereof, can also be used as monomers. The range of non-natural (unnatural) amino acids that can be incorporated into such compositions is well known to those skilled in the art (Zhang et al. (2013), Current Opinion in Structural Biology 23, pp. 581-587; incorporated by reference in its entirety for all purposes). In some embodiments, the biodegradable polymer is used as a co-monomer, i.e., in a mixture of monomers. In some embodiments, the biodegradable polymer is a bifunctional monomer.

[0084] In some embodiments, the particles are engineered to degrade to provide biomolecules to a cell in culture. Degradation can include, without limitation, dissolution (i.e., dissolving) or lysis. The particle can be engineered to have multiple layers, with different rates of degradation for at least two of the layers. The particle, whether in its entirety or various layers thereof, can be degraded chemically (e.g., reagents, detergents, bursting, or the like), mechanically (e.g., vibration, acoustic, freeze-thaw, bursting, or the like), or both chemically and mechanically.Docket No. SLIN-032 / 01WO 217N-432617-WO

[0085] The rate of degradation of the entire particles, individual layers of the particles, or groups or subpopulations of a particle population can be fast (i.e., less than 24 hours) or slow (i.e., 24 hours or more). For example, a first layer of a particle can degrade in less than 24 hours and a second layer of the same particle can degrade in 48 hours. As yet another example, a first subpopulation of particles can degrade in less than 1 hour, a second subpopulation of particles can degrade in 24 hours, and a third subpopulation of particles can degrade in one week. The first, second, and third subpopulations form a population of particles.

[0086] In some embodiments, a population of particles can include groups or subpopulations of particles having different rates of degradation.

[0087] In some embodiments, the particle can be engineered to have pore sizes which correlate to various rates of degradation. The pore sizes can range from 0.1 nm to 1 pm. For example, a first particle can have a first pore size, such that the first particle has a first rate of degradation; and, a second can have a second pore size, such that the particle has a second rate of degradation with the first and second rates of degradation not being equal (e.g., first rate is faster than the second rate; or the first rate is slower than the second rate).

[0088] In some embodiments, the particle can be engineered to have a rate of degradation based on a plurality of factors, including, without limitation, pore size, chemical composition (i.e., chemical bonds, monomers, co-monomer), layer composition, the like, and combinations thereof.

[0089] In some embodiments, the particle contains disulfide crosslinks enabling the particle to dissolve upon the addition of a reducing agent. In some embodiments, the particle can be dissolved by the addition of a protease. In some embodiments, the growth factors are crosslinked to each other or to the matrix via disulfide crosslinks that may be broken by the addition of a reducing agent, releasing active growth factors. Appropriate reducing agents may include but are not limited to dithiothreitol, Tris(2-carboxyethyl)phosphine hydrochloride, and 2 -mercaptoethanol. In some embodiments, the particle comprises only one type of molecule that supports cell growth and / or stimulates target cell proliferation or activation. In some embodiments, the particle comprises only one class of molecule that supports target cell growth and / or stimulates target cell proliferation or activation. In some embodiments, the particle comprises multiple types and / or classes of molecules that support cell growth and / or stimulate target cell proliferation or activation.Docket No. SLIN-032 / 01WO 217N-432617-WOPolymerization and Functionalization of Synthetic Particles

[0090] In some embodiments, the synthetic particles provided herein are synthesized by polymerizing one or more of the monomers of the present disclosure. The synthesis is carried out to form individual particles. In some embodiments, the monomeric material (monomer) is polymerized to form a homopolymer. In some embodiments, copolymers of different monomeric units (i.e., co-monomers) are synthesized and used in the methods provided herein. In some embodiments, the monomer or co-monomers used in the methods and compositions described herein is a bifunctional monomer or includes a bifunctional monomer (where comonomers are employed). The use of bifunctional monomers allows for tire further derivatization of particles, e.g., with biomolecules, cell surface markers or epitope binding fragments thereof, or a combination thereof. In some embodiments, the particle is synthesized in the presence of a crosslinker. In some embodiments, the particle is synthesized in the presence of a polymerization initiator.

[0091] The amoun t of monomer can be varied by the user, for example to obtain a particular optical property that is substantially similar to that of a target cell. In some embodiments, the monomeric component(s) (i.e., monomer, co-monomer, bifunctional monomer, or a combination thereof, for example, bis / acrylamide in various crosslinking ratios, allyl amine or other co-monomers which provide chemical functionality for secondary labeling / conjugation, or alginate) is present at about 10 percent by weight to about 95 percent weight of the particle. In some embodiments, the monomeric component(s) is present at about 15 percent by weight to about 90 percent weight of the particle, or about 20 percent by weight to about 90 percent weight of the particle.

[0092] Examples of various monomers and cross-linking chemistries available for use with the present disclosure are provided in the Thermo Scientific Crosslinking Technical Handbook entitled “Easy molecular bonding crosslinking technology” (available at tools.lifetechnologies.com / content / sfs / brochures / 1602163-Crosslinking-Reagents-Handbook.pdf), the disclosure of which is incorporated by reference in its entirety for all purposes. For example, hydrazine (e.g., with an NHS ester compound) or EDC coupling reactions (e.g., with a maleimide compound) can be used to construct the particles of the disclosure.

[0093] In some embodiments, a monomer for use with the particles provided herein is lactic acid, glycolic acid, acrylic acid, 1 -hydroxyethyl methacrylate, ethyl methacrylate, 2- hydroxyethyl methacrylate (HEMA), propylene glycol methacrylate, acrylamide, N- vinylpyrrolidone (NVP), methyl methacrylate, glycidyl methacrylate, glycerol methacrylateDocket No. SLIN-032 / 01WO 217N-432617-WO(GMA), glycol methacrylate, ethylene glycol, fumaric acid, a derivatized version thereof, or a combination thereof. In some embodiments, the polymer may be degradable. For instance, the polymer may be a polyester based on polylactide (PLA), polyglycolide (PGA), polycaprolactone, poly(lactic-co-glycolic) acid (PLGA), or their copolymers. Other biodegradable polymers may be used.

[0094] In some embodiments, one or more of the following monomers is used herein to form a particle of the present disclosure: 2 -hydroxyethyl methacrylate, hydroxyethoxy ethyl methacrylate, hydroxydiethoxyethyl methacrylate, methoxyethyl methacrylate, methoxy ethoxy ethyl methacrylate, methoxy diethoxy ethyl methacrylate, poly (ethylene glycol) methacrylate, methoxy-poly (ethylene glycol) methacrylate, methacrylic acid, sodium methacrylate, glycerol methacrylate, hydroxypropyl methacrylate, hydroxybutyl methacrylate, or a combination thereof.

[0095] In some embodiments, one or more of the following monomers is used herein to form a tunable particle: phenyl acry late, phenyl methacrylate, benzyl acry late, benzyl methacry late, 2 -phenylethyl acrylate, 2 -phenylethyl methacrylate, 2 -phenoxyethyl acrylate, 2 -phenoxy ethyl methacrylate, phenylthioethyl acrylate, phenylthioethyl methacrylate, 2,4,6-tribromophenyl acrylate, 2,4,6-tribromophenyl methacrylate, pentabromophenyl acrylate, pentabromophenyl methacrylate, pentachlorophenyl acrylate, pentachlorophenyl methacrylate, 2,3- dibromopropyl acrylate, 2,3-dibromopropyl methacrylate, 2-naphthyl acrylate, 2-naphthyl methacrylate, 4-methoxybenzyl acrylate, 4-methoxybenzyl methacrylate, 2 -benzyloxy ethyl acrylate, 2-benzyloxyethyl methacrylate, 4-chlorophenoxyethyl acrylate, 4-chlorophenoxyethyl methacrylate, 2-phenoxyethoxyethyl acrylate, 2-phenoxyethoxyethyl methacrylate, N-phenyl acrylamide, N-phenyl methacrylamide, N-benzyl acrylamide, N- benzyl methacrylamide, N, N-dibenzyl acrylamide, N, N-dibenzyl methacrylamide, N-diphenylmethyl acrylamide N-(4-methylphenyl)methyl acrylamide, N-l-naphthyl acrylamide, N-4-nitrophenyl acry lamide, N-(2-phenylethyl)acrylamide, -triphenylmethyl acrylamide, N-(4-hydroxyphenyl)acrylamide, N, N-methylphenyl acrylamide, N, N-phenyl phenylethyl acry lamide, N-diphenylmethyl methacrylamide, N-(4-methyl phenyl)methyl methacrylamide, N-l-naphthyl methacrylamide, N-4-nitrophenyl methacrylamide, N-(2-phenylethyl)methacrylamide, -triphenylmethyl methacrylamide, N-(4-hydroxyphenyl)methacrylamide, N, N-methylphenyl methacrylamide, N, N'-phenyl phenylethyl methacrylamide, N-vinylcarbazole, 4-vinylpyridine, 2-vinylpyridine, as described in U. S. Patent No. 6,657,030, which is incorporated by reference in its entirety herein for all purposes.Docket No. SLIN-032 / 01WO 217N-432617-WO

[0096] Both synthetic monomers and bio-monomers can be used in the particles provided herein, to form synthetic particles. In some embodiments, the synthetic particles may comprise a chemical component and a bio-component (e.g., peptide, protein, monosaccharide, disaccharide, polysaccharide, primary amines sulfhydryls, carbonyls, carbohydrates, carboxylic acids present on a biomolecule). For example, proteins, peptides or carbohydrates can be used as individual monomers to form a particle that includes or does not include a synthetic monomer (or polymer) and in combination with chemically compatible co-monomers and crosslinking chemistries (see, e.g., the Thermo Scientific Crosslinking Technical Handbook entitled “Easy molecular bonding crosslinking technology,’’ available at tools.lifetechnologies.com / content / sfs / brochures / 1602163-Crosslinking-Reagents-Handbook.pdf, the disclosure of which is incorporated by reference in its entirety for all purposes). Compatible crosslinking chemistries include, but are not limited to, amines, carboxyls, and other reactive chemical side groups. Representative reactive groups amenable for use in the particles and monomers described herein are provided in Table 2, below.Table 2 Crosslinker reactive groups amenable for bio-inonomer conjugation Reactivity class Target functional Reactive chemical group groupAmine reactive -NH2NHS esterImidoester Pentafluorophenyl ester Hydroxymethyl phosphine Carboxyl-to-amine reactive -COOH Carbodiimide (e.g., EDC) Sulfhydryl-reactive -SH MaleimideHaloacetyl (bromo- or iodo-) Pyridyldisulfide Thiosulfonate VinylsulfonateAldehyde-reactive (oxidized sugars, -CHO Hydrazinecarbonyls) Alkoxy aminePhoto-reactive (e.g., nonselective, random) Random Diazirineinsertion) Aryl azideHydroxyl (nonaqueous)-reactive -OH IsocyanateAzide-reactive -N3PhosphineDocketNo. SLIN-032 / 01WO 217N-432617-WO

[0097] In general, any form of polymerization chemistry / methods known by those skilled in the art can be employed to form polymers. In some embodiments, polymerization can be catalyzed by ultraviolet light-induced radical formation and reaction progression. In other embodiments, a particle of the disclosure is produced by the polymerization of acrylamide or the polymerization of acrylate. For example, the acrylamide in some embodiments is a polymerizable carbohydrate derivatized acrylamide as described in U. S. Patent No. 6,107,365, the disclosure of which is incorporated by reference in its entirety for all purposes. As described therein and known to those of ordinary skill in the art, specific attachment of acrylamide groups to sugars is readily adapted to a range of monosaccharides and higher order polysaccharides, e.g., synthetic polysaccharides or polysaccharides derived from natural sources, such as glycoproteins found in serum or tissues.

[0098] In some embodiments, an acrylate -functionalized poly(ethylene) glycol monomer is used as a monomer. For example, the PEG In some embodiments is an acrylate or acrylamide functionalized PEG.

[0099] In some embodiments, a particle comprises a monofunctional monomer polymerized with at least one bifunctional monomer. One example includes, but is not limited to, the formation of poly-acrylamide polymers using acry lamide and bis-acrylamide (a bifunctional monomer). In some embodiments, a particle provided herein comprises a bifunctional monomer polymerized with a second bifunctional monomer. One example includes, but is not limited to, the formation of polymers with mixed composition containing compatible chemistries such as acrylamide, bis-acrylamide, and bis-acrylamide structural congeners containing a wide range of additional chemistries. The range of chemically compatible monomers, bifunctional monomers, and mixed compositions is obvious to those skilled in the art and follows chemical reactivity principles know to those skilled in the art. See, e.g., the Thermo Scientific Crosslinking Technical Handbook entitled “Easy molecular bonding crosslinking technology” (available at tools.lifetechnologies.com / content / sfs / brochures / 1602163-Crosslinkmg-Reagents-Handbook.pdf) and the Polyacrylamide Emulsions Handbook (SNF Floerger, available at snf.com.au / do-wnloads / Emulsion__Handbook__E.pdf), the disclosure of each of which is incorporated by reference in its entirety for all purposes.

[0100] In some embodiments, a particle provided herein comprises a polymerizable monofunctional monomer and is a monofunctional acrylic monomer. Non-limiting examples of monofunctional acry lic monomers for use herein are acrylamide; methacrylamide; N- alkylacrylamides such as N -ethylacrylamide, N-isopropylacrylamide or N-tert-butylacrylamide; N -alkylmethacrylamides such as N-ethylmethacrylamide or N-Docket No. SLIN-032 / 01WO 217N-432617-WOisopropylmethacrylamide; N, N-dialkylacrylamides such as N, N-dimethylacrylamide and N, N-diethyl-acrylamide; N-[(dialkylamino)alkyl] -acrylamides such as N-[3dimethylamino)-propyl] -acrylamide or N-[3-(diethylamino)propyl]-acrylamide; N-[(dialkylamino)alkyl]-methacrylamides such as N-[3-dimethylamino)propyl] methacrylamide or N-[3-(diethyiamino) propyl] methacrylamide; (dialkylamino)alkyl acrylates such as 2-(dimethylamino )ethyl acrylate, 2-( dimethylamino)propyl acrylate, or 2 -(diethyl am inojethyl acrylates: and (dialkylamino) alkyl methacrylates such as 2-(dimethylamino) ethyl methacrylate.

[0101] A bifunctional monomer is any monomer that can polymerize with a monofunctional monomer of the disclosure to form a particle as described herein that further contains a second functional group that can participate in a second reaction, e.g., conjugation of a fluorophore, cell surface receptor (or domain thereof), or immune co-stimulatory or adhesion biomolecule.

[0102] In some embodiments, a bifunctional monomer is selected from the group consisting of allyl amine, allyl alcohol, allyl isothiocyanate, allyl chloride, and allyl maleimide.

[0103] A bifunctional monomer can be a bifunctional aery lie monomer. Non-limiting examples of bifunctional acrylic monomers are N, N'-methylenebisacrylamide, N, N'-methylene bismethacrylamide, N. N' -ethylene bisacrylamide, N, N'-ethylene bismethacrylamide, N, N'-propylenebisacrylamide, and N, N'-(l,2-dihydroxyethylene) bisacrylamide.

[0104] Higher order branched chain and linear co-monomers can be substituted in the polymer mix to adjust the refractive index while maintaining polymer density, as described in U. S. Patent No. 6,657,030, which is incorporated herein by reference in its entirety for all purposes.

[0105] In some embodiments, a particle comprises a molecule that modulates the optical properties of the particle.

[0106] In some embodiments, the biomonomer is functionalized with acry lamide or acrylate. For example, in some embodiments, the polymerizable acrylamide functionalized biomolecule is an acrylamide or acrylate functionalized protein (for example, an acrylamide functionalized collagen or fiinctionalized collagen domain), an acrylamide or acrylate functionalized peptide, or an acrylamide or acrylate functionalized monosaccharide, disaccharide or polysaccharide.

[0107] Any monosaccharide, disaccharide or polysaccharide (functionalized or otherwise) can be used. In some embodiments, an acrylamide or acrylate functionalized monosaccharide, disaccharide or polysaccharide is used as a polymerizable monomer. In some embodiments, a structural polysaccharide is used as a polymerizable monomer. In some embodiments, the structural polysaccharide is an arabinoxylan, cellulose, chitin or a pectin. In some embodiments, alginic acid (alginate) is used as a polymerizable monomer. In yet anotherDocket No. SLIN-032 / 01WO 217N-432617-WOembodiment, a glycosaminoglycan (GAG) is used as a polymerizable monomer in the particles provided herein. In some embodiments, the GAG is chondroitin sulfate, dermatan sulfate, keratin sulfate, heparin, heparin sulfate or hyaluronic acid (also referred to in the art as hyaluron or hyaluronate) is used as a polymerizable monomer. The additional range of compatible biomonomers and their reactive chemistries are known be individuals skilled in the art and follow general chemical reactivity principles.

[0108] An additional range of biocompatible monomers that can be incorporated are known in the art, see, for example the non-degradable biocompatible monomers disclosed in Shastri (2003), Current Pharmaceutical Biotechnology 4, pp. 331-337, incorporated by reference herein in its entirety for all purposes. Other monomers are provided in de Moraes Porto (2012), Polymer Biocompatibility, Polymerization, Dr. Ailton De Souza Gomes (Ed.), ISBN: 978-953- 51-0745-3; InTech, DOI: 10.5772 / 47786; Heller et al. (2010), journal of Polymer Science Part A: Polymer Chemistry 49, pp. 650-661; Final Report for Biocompatible Materials (2004), The Board of the Biocompatible Materials and the Molecular Engineering in Polymer Science programmes, ISBN 91-631-4985-0, the disclosure of each of which is hereby incorporated by reference in its entirety for all puiposes.

[0109] Biocompatible monomers for use with the particles described herein include in some embodiments, ethylene glycol dimethacrylate (EGDMA), 2-hydroxyethyl methacrylate (HEMA), methyl methacrylate (MMA), methacryloxymethyltrimethylsilane (TMS-MA), N-vinyl-2-pyrrolidon (N-VP), styrene, or a combination thereof.

[0110] Naturally occurring particles useful in this disclosure include various polysaccharides available from natural sources such as plants, algae, fungi, yeasts, marine invertebrates and arthropods. Non-limiting examples include agarose, dextrans, chitin, cellulose-based compounds, starch, derivatized starch, and the like. These generally will have repeating glucose units as a major portion of the polysaccharide backbone. Cross-linking chemistries for such polysaccharides are known in the art, see for example Thermo Scientific Crosslinking Technical Handbook entitled “Easy molecular bonding crosslinking technology” (available at tools.lifetechnologies.com / content / sfs / brochures / I602163-Crosslinking-Reagents-Handbook.pdf).

[0111] Hyaluronan in some embodiments is used as a monomer (either as a single monomer or as a co-monomer). In some embodiments, hyaluronan is functionalized, for example with acrylate or acrylamide. Hyaluronan is a high molecular weight GAG composed of di saccharide repeating units of N-acetylglucosamine and glucuronic acid linked together through alternating [3-1,4 and (3-1,3 glycosidic bonds. In the human body, hyaluronate is found in several softDocket No. SLIN-032 / 01WO 217N-432617-WOconnective tissues, including skin, umbilical cord, synovial fluid, and vitreous humor. Accordingly, in some embodiments, where one or more properties of a skin cell, umbilical cord cell or vitreous humor cell is desired to be mimicked, in some embodiments, hyaluronan is used as a monomer. Methods for fabricating particles are described in Xu et al. (2012), Soft Matter, 8, pp. 3280-3294, the disclosure of which is incorporated herein in its entirety for all purposes. As described therein, hyaluronan can be derivatized with various reactive handles depending on the desired cross-linking chemistry and other monomers used to form a particle.

[0112] In some embodiments, chitosan, a linear polysaccharide composed of randomly distributed p-(l-4)-linked D-glucosamine (deacetylated unit) and N-acetyl-D-glucosamine (acetylated unit), is used as a monomer (either as a single monomer or as a co-monomer).

[0113] Other polysaccharides for use as a monomer or co-monomer include but are not limited to, agar, agarose, alginic acid, alguronic acid, alpha glucan, amylopectin, amylose, arabinoxylan, beta-glucan, callose, capsulan, carrageenan polysaccharides (e.g., kappa, iota or lambda class), cellodextrin, cellulin, cellulose, chitin, chitosan, chrysolaminarin, curdlan, cyclodextrin, alpha-cyclodextrin, dextrin, ficoll, fructan, fucoidan, galactoglucomannan, galactomannan, galactosamino galactan, gellan gum, glucan, glucomannan, glucorunoxylan, glycocalyx, glycogen, hemicellulose, homopolysaccharide, hypromellose, icodextrin, inulin, kefiran, laminarin, lentinan, levan polysaccharide, lichenin, mannan, mixed-linkage glucan, paramylon, pectic acid, pectin, pentastarch, phytoglycogen, pleuran, polydextrose, polysaccharide peptide, porphyran, pullulan, schizophyllan, sinistrin, sizofiran, welan gum, xanthan gum, xylan, xyloglucan, zymosan, or a combination thereof. As described throughout, depending on the desired cross-linking chemistry and / or additional co-monomers employed in the particle, the polysaccharide can be further functionalized. For example, one or more of the polysaccharides described herein in some embodiments is functionalized with acry ate or acrylamide.

[0114] In some embodiments, an individual particle or a plurality- thereof comprises a peptide, protein, a protein domain, or a combination thereof as a monomer or plurality thereof. In some embodiments, the protein is a structural protein, or a domain thereof, for example, such as silk, elastin, titin or collagen, or a domain thereof. In some embodiments, the protein is an extracellular matrix (ECM) component (e.g., collagen, elastin, proteoglycan, fibrin, lysine, fibronectin). In some embodiments, the structural protein is collagen. In some embodiments, the collagen is collagen type I, collagen type II or collagen type III or a combination thereof, in some embodiments, the monomer comprises a proteoglycan. In some embodiments, theDocket No. SLIN-032 / 01WO 217N-432617-WOproteoglycan is decorin, biglycan, testican, bikunin, fibromodulin, lumican, or a domain thereof.

[0115] In some embodiments, an acrylate-functionalized structural protein monomer is used as a component of the particle provided herein (e.g., an acrylate functionalized protein or protein domain, for example, silk, elastin, titin, collagen, proteoglycan, or a functionalized domain thereof). In some embodiments, the acrylate functionalized structural protein monomer comprises a proteoglycan, e.g., decorin, biglycan, testican, bikunin, fibromodulin, lumican, or a domain thereof.

[0116] In some embodiments, PEG monomers and oligopeptides can be that mimic extracellular matrix proteins are used in the particles provided herein, for example, with vinyl sulfone-functionalized multi arm PEG, integrin binding peptides and bis-cysteine matrix metalloproteinase peptides as described by Lutolf et al. (2003), Proc, Natl. Acad. Sci. U. S. A.100, 5413-5418, incorporated by reference in its entirety’ for all purposes. In some embodiments, particles are formed by a Michael-type addition reaction between the di- thiolated oligopeptides and vinyl sulfone groups on the PEG. The range of additional compatible chemistries that can be incorporated here are apparent to those skilled in the art and follow general chemical reactivity principles, see for example Thermo Scientific Crosslinking Technical Handbook entitled “Easy molecular bonding crosslinking technology” (available at tools.lifetechnologies.com / content / sfs / brochures / 1602163-Crosslinking-Reagents-Handbook.pdf).

[0117] Other bioactive domains in natural proteins can also be used as a monomer or portion thereof. For example, a cell-adhesive integrin binding domain, a controlled release affinity binding domain or a transglutaminase cross-linking domain can be used in the particles provided herein. Details for producing such particles can be found in Martino et al. (2009), Biomaterials 30, 1089; Martino et al. (2011), Sci. Trans. Med. 3, 100ra89; Hu and Messersmith (2003), J. Am. Chem. Soc. 125, 14298, each of which is incorporated by reference in its entirety for all purposes.

[0118] In some embodiments, recombinant DNA methods are used to create proteins, designed to gel in response to changes in pH or temperature, for example, by the methods described by Petka et al. (1998), Science 281, pp. 389-392, incorporated by reference in its entirety for all purposes. Briefly, the proteins consist of terminal leucine zipper domains flanking a water-soluble polyelectrolyte segment. In near-neutral aqueous solutions, coiled-coil aggregates of the terminal domains form a three-dimensional polymer network.Docket No. SLIN-032 / 01WO 217N-432617-WO

[0119] Common crosslinking agents that can be used to crosslink the particles provided herein include but are not limited to ethylene glycol dimethacrylate (EGDMA), tetra ethylene glycol dimethacrylate, and N, N'-15 methylenebisacrylamide. The range of additional crosslinking chemistries which can be used will be apparent to those skilled in the art and follow general chemical reactivity principles, see for example Thermo Scientific Crosslinking Technical Handbook entitled "‘Easy molecular bonding crosslinking technology” (available at tools.lifetechnologies.com / content / sfs / brochures / 1602163-Crosslinking-Reagents-Handbook.pdf).

[0120] In some embodiments, polymerization of a monomer is initiated by a persulfate or an equivalent initiator that catalyzes radical formation. The range of compatible initiators are known to those skilled in the art and follow general chemical reactivity principles, see for example Thermo Scientific Crosslinking Technical Handbook entitled “Easy molecular bonding crosslinking technology” (available at tools.lifetechnologies.com / content / sfs / brochures / 1602163-Crosslinking-Reagents-Handbook.pdf). The persulfate can be any water-soluble persulfate. Non-limiting examples of water-soluble persulfates are ammonium persulfate and alkali metal persulfates. Alkali metals include lithium, sodium and potassium. In some embodiments, the persulfate is ammonium persulfate or potassium persulfate. In some embodiments, polymerization of the monomer provided herein is initiated by ammonium persulfate.

[0121] Polymerization of a monomer can be accelerated by an accelerant which can catalyze the formation of polymerization-labile chemical side groups. The range of possible accelerants is known to those skilled in the art and follow' general chemical reactivity principles. See for example Thermo Scientific Crosslinking Technical Handbook entitled “Easy molecular bonding crosslinking technology” (available at tools.lifetechnologies.com / content / sfs / brochures / 1602163-Crosslinking-Reagents-Handbook.pdf). In some embodiments, the accelerant is a tertiary amine. The tertiary amine can be any water-soluble tertiary amine. In some embodiments, an accelerant is used in the polymerization reaction and is 3-(dimethylamino) propionitrile, or N, N, N', N'tetramethylethylenediamine (TEMED). In some embodiments, an accelerant is used in the polymerization reaction and is azobis(isobutyronitrile) (AIBN).

[0122] As discussed above, the particle for use in the compositions and methods described herein can include any of the monomeric units and crosslinkers as described herein, and in some embodiments are produced as particles by polymerizing droplets. Microfluidic methods of producing a plurality of droplets, including fluidic and rigidified droplets, are known to thoseDocket No. SLIN-032 / 01WO 217N-432617-WOof ordinary skill in tlie art. and described in US Patent Publication No. 2011 / 0218123 and U. S. Patent No. 7,294,503, each incorporated herein by reference in its entirety for all purposes. Such methods provide for a plurality of droplets containing a first fluid (e.g., dispersed phase) and being substantially surrounded by a second fluid (e.g., a continuous phase), where the first fluid and the second fluid are substantially immiscible (e.g., droplets containing an aqueous¬ based liquid being substantially surrounded by an oil-based liquid),

[0123] A plurality of fluidic droplets (e.g., prepared using a microfluidic device) may be polydisperse (e.g., having a range of different sizes), or in some cases, the fluidic droplets may be monodisperse or substantially monodisperse, e.g., having a homogenous distribution of diameters, for instance, such that no more than about 10%, about 5%, about 3%, about 1%, about 0.03%, or about 0.01% of the droplets have a diameter that is about 10%, about 5%, about 3 %, or about 1 % greater than the average diameter. The average diameter of a population of droplets, as used herein, refers to the arithmetic average of the diameters of the droplets. Average diameters of the particles can be measured, for example, by light scattering techniques. In some embodiments, average diameters of particles are tailored, for example by varying flow rates of the fluid streams of the first and second fluids within the channel(s) of a microfluidic device, or by varying the volume of the channel(s) of the microfluidic device.

[0124] Accordingly, the disclosure provides population of particles comprising a plurality of particles, wherein the population of particles is substantially monodisperse.

[0125] The term “microfluidic” refers to a device, apparatus or system including at least one fluid channel having a cross-sectional dimension of less than 1 mm, and a ratio of length to largest cross-sectional dimension perpendicular to the channel of at least about 3:1. A microfluidic device comprising a microfluidic channel is especially well suited to preparing a plurality of monodisperse droplets.

[0126] Non-limiting examples of microfluidic systems that may be used with the present disclosure are disclosed in U. S. Patent Application Publication No. 2006 / 0163385; U. S. Patent Application Publication No. 2005 / 0172476; U. S. Patent Application Publication No.2007 / 000342; International Patent Application Publication No. WO 2006 / 096571; U. S. Patent Application Publication No. 2007 / 0054119; U. S. Patent No. 7,776,927; and International Patent Application Publication No. WO 2006 / 078841, each incorporated herein by reference in its entirety for all pwposes.

[0127] Droplet size is related to microfluidic channel size. The microfluidic channel may be of any size, for example, having a largest dimension perpendicular to fluid flow of less than about 5 mm or 2 mm, or less than about 1 mm, or less than about 500 pm, less than about 200 pm,Docket No. SLIN-032 / 01WO 217N-432617-WOless than about 100 pm, less than about 60 pm, less than about 50 um, less than about 40 pm, less than about 30 pm, less than about 25 pm, less than about 10 pm, less than about 3 pm, less than about 1 pm, less than about 300 nm, less than about 100 nm, less than about 30 nm, or less than about 10 nm.

[0128] Droplet size can be tuned by adjusting the relative flow rates. In some embodiments, drop diameters are equivalent to the width of the channel, or within about 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% the width of the channel.

[0129] In some embodiments, the dimensions of a particle of the disclosure are substantially similar to the droplet from which it was formed. Therefore, in some embodiments, a particle has a diameter of less than about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 120, 150, 200, 250, 300, 350, 400, 450, 500, 600, 800, or 1000 pm in diameter, including all ranges and subranges therebetween. In some embodiments, a particle has a diameter of more than about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 120, 150, 200, 250, 300, 350, 400, 450, 500, 600, 800, or 1000 pm in diameter. In some embodiments, a particle has a diameter in the range of 5 pm to 100 pm, including all ranges and subranges therebetween.

[0130] In some embodiments, particle manufacturing is earned out by suspension polymerization, which is also referred to in the art as pearl, bead or granular polymerization (see Elbert (2011), Acta Biomater. 7, pp. 31-56, incorporated by reference herein in its entirety for all purposes). In suspension polymerization, the monomer is insoluble in the continuous phase, for example an aqueous monomer solution in a continuous oil phase. In suspension polymerization, polymerization initiation occurs within the monomer-rich droplets and with greater than one radical per droplet at any time. In some embodiments, the monomer phase includes a monomer which can be a bifunctional monomer or a plurality of monomer species (co-monomers, which can be a plurality of bifunctional monomers). In some embodiments, the monomer phase includes an initiator and / or a crosslinking agent.

[0131] Emulsion polymerization can also be used to form the particles described herein. In emulsion polymerization, the monomer has poor solubility in the continuous phase, similar to suspension polymerization, however, polymerization initiation occurs outside the monomer droplets (see Elbert (2011), Acta Biomater. 7, pp. 31-56, incorporated by reference herein in its entirety for all purposes). In emulsion polymerization embodiments, the initiator causes chain growth of the monomer (or co-monomers) dissolved in the continuous phase or monomer contained in micelles if surfactants are present.Docket No. SLIN-032 / 01WO 217N-432617-WO

[0132] In some embodiments, particles are formed by precipitation polymerization, for example as described in Elbert (2011), Acta Biomater. 7, pp. 31-56, incorporated by reference herein in its entirety for all purposes. Precipitation polymerization is a technique that takes advantage of the differences in the solubility of monomer and polymer to produce microparticles. Specifically, it is known that larger polymer chains generally have lower solubility than smaller ones. Accordingly, above a specific molecular weight, phase separation may be favored. Precipitation polymerization initially begins as solution polymerizations in a single phase, homogenous system. In some embodiments, shortly after the start of the polymerization, a relatively high concentration of polymer chains is present, favoring phase separation by nucleation. As polymerization proceeds, the concentration of polymer chains is low and existing particles capture the chains before nucleation of new particles can occur. Tirus, nucleation of particles occurs only for a brief period of time shortly after tire start of the reaction, which, in some embodiments, results in a narrow size distribution of particles. Additional methods include but are not limited to lithographic particle formation (Helgeson et al. (2011), Curr. Opin. Colloid. Interface Sci. 16, pp. 106-117, incorporated by reference herein in its entirety for all purposes), membrane emulsification (e.g., by the microsieve emulsification technology techniques described by Nanomi B. V. (Netherlands)), microchannel emulsification (Sugiura et al. (2002), Langmuir 18, pp. 5708-5712, incorporated by reference herein in its entirety) and bulk emulsification (SNF Floerger, available at snf.com.au / downloads / Emulsion_Handbook_E.pdf, incoqjorated by reference herein in its entirety).

[0133] In some embodiments, particles are formed within a microfluidic device having two oil channels that focus on a central stream of aqueous monomer solution. In some embodiments, droplets form at the interface of the two channels and central stream to break off droplets in water-in-oil emulsion. In some embodiments, once droplets are formed, they are stabilized prior to polymerization, for example, by adding a surfactant to the oil phase. However, in some embodiments, droplets are not stabilized prior to polymerization. In some embodiments, polymerization of the monomer is triggered by adding an accelerator (e.g., N, N, N’, N’- tetramethylethylenediamine) to one or both of the oil channels after initial droplets are formed.

[0134] The aqueous monomer solution as provided above can include a single monomer species or a plurality of monomer species. The aqueous monomer solution can include comonomers, a bifunctional monomer, or a combination thereof. In some embodiments, the monomer or plurality of monomers can include a bifunctional monomer, for example, one ofDocket No. SLIN-032 / 01WO 217N-432617-WOthe monomers described herein. In some embodiments, co-monomers can be used to modulate forward scatter or side scatter, for example, by adjusting the refractive index of the particle.

[0135] In some embodiments, tire central stream of aqueous monomer solution comprises a cross-linker, for example, N, N'-bisacrylamide. In some embodiments, the central stream of aqueous monomer solution comprises a cross-linker and an accelerator, in addition to the monomer. In some embodiments, the aqueous monomer solution comprises an initiator, for example an oxidizing agent such as ammonium persulfate.

[0136] In some embodiments, forward scatter is modulated by adjusting the refractive index of the gel by adding co-monomers allyl acrylate and allyl methacrylate. Forw ard scatter can also be modulated with side scattering nanoparticles containing sufficient optical resolution / size / density including, but not limited to, higher density colloidal suspensions of silica and / or PMMA particles. Side scattering of the droplets can be tuned by adding a colloidal suspension of silica nanoparticles and / or PMMA (poly(methyl methacrylate)) particles (-100 nm) to the central aqueous phase prior to polymerization.

[0137] In some embodiments, a bead, plurality of beads, biomolecule, or plurality of biomolecules is embedded (encapsulated) within the particle. In some embodiments, an encapsulated bead or biomolecule is employed to mimic one or more intracellular organelles of a target cell, or a cell after it engulfs a particle. In some embodiments, encapsulating or embedding a bead or biomolecule is accomplished at the time of particle formation. For example, beads can be suspended in the appropriate concentration to allow for an average of one bead to be embedded / encapsulated in a single particle. The bead suspension can be included, for example, within the aqueous solution of monomer. Similarly, a biomolecule or mixture of biomolecules can be incorporated into the aqueous solution of monomer to encapsulate the biomolecule or biomolecules,

[0138] In some embodiments, once a particle is formed, for example by the methods described above, it can be further manipulated, for example, by embedding a bead, plurality of beads, biomolecule or plurality of biomolecules within the particle,

[0139] Accordingly, in some embodiments of the disclosure, a particle comprising an embedded substance is provided.

[0140] In some embodiments, the embedded substance is an embedded molecule, for example a biomolecule. The biomolecule can be a single species or a plurality of different species. For example, a protein, peptide, carbohydrate, nucleic acid or combination thereof can be encapsulated within a particle of the disclosure. Moreover, different nucleic acid molecules (e.g., of varying sequences or nucleic acid type such as genomic DNA, messenger RNA orDocket No. SLIN-032 / 01WO 217N-432617-WODNA-RNA hybrids) can be encapsulated by the particle of the disclosure. These can be comprised of any protein or nucleic acid as both forms of biological material contain labile chemical side-groups (or can be modified by commercial vendors (e.g., Integrated DNA Technology chemical side group modifications). Such side-groups are compatible with reaction chemistries commonly found in co-monomer compositions (e.g., acrylate chemistry, NHS-ester, primary’ amines, copper catalyzed click chemistry (Sharpless)). The range of possible embedded molecules which contain compatible chemistries is understood by those skilled in the art. In some embodiments, embedded molecules can also be attached on particle surfaces, including micro and / or macropore surfaces.

[0141] In some embodiments, different subpopulations of particles are fabricated, each with a different concentration of biomolecule. In some embodiments, the biomolecule is a nucleic acid, a protein, an intracellular ion such as calcium acid (or other biomolecule of the user’s choosing, for example, calcium). In some embodiments, different subpopulations of particles are fabricated, each with a different concen tration of a drug substance. In some embodiments, the drug substance is a biomolecule (i.e., a biologic, antibody or antigen-binding fragment thereof, antibody drug conjugate, protein / enzyme, peptide, non-ribosomal peptide, or related molecule) or a small molecule synthetic drug (e.g., Type I / II / III polyketide, non-ribosomal peptide with bioactive properties, or other small molecule entity as generally classified by those skilled in the art).

[0142] In some embodiments, a particle of the disclosure has material modulus properties (e.g., elasticity) more closely resembling that of a target cell as compared to a polystyrene bead of the same diameter.

[0143] After the particle is formed, one or more of tire particle's surfaces can be functionalized, for example, to mimic one or more optical properties of a target cell or a labeled target cell, or to imbue the particle with immunostimulatory properties. Tire functionalized particle can also include an embedded bead or substance such as a biomolecule, as described above. In some embodiments, one or more particles are functionalized with one or more fluorescent dyes, one or more cell surface markers / immune co-stimulatory or adhesion biomolecules (or epitope binding regions thereof), or a combination thereof. In some embodiments, the particle is formed by polymerizing at least one bifunctional monomer and after formation, the particle includes one or more functional groups that can be used for further attachment of a cell surface marker, an epitope binding region of a cell surface marker, a fluorescent dye, or combination thereof. In some embodiments, the free functional group is an amine group, a carboxyl group, a hydroxyl group, or a combination thereof. Depending on the functionalization desired, it is toDocketNo. SLIN-032 / 01WO 217N-432617-WObe understood that multiple bifunctional monomers can be used, for example, to functionalize the particle, for example using different chemistries and with different molecules.

[0144] A particle can be functionalized with any fluorescent dye known in the art, including fluorescent dyes listed in The Molecular Probes Handbook-A Guide to Fluorescent Probes and Labeling Technologies, incorporated herein by reference in its entirety for all purposes. Functionalization can be mediated by a compound comprising a free amine group, e.g,, allylamine, which can be incorporated into a bifunctional monomer used to form the particle, as discussed herein.

[0145] Non-limiting examples of known fluorescent dyes that can be used to functionalize the surface of a particle described herein include: 6-carboxy-4', 5'-dichloro- 2', 7'-dimethoxyfluorescein succinimidylester; 5-(6)-carboxyeosin; 5- carboxyfluorescein;6 carboxyfluorescein; 5-(6)-carboxyfluorescein; S-carboxyfluorescein- bis-(5-carboxymethoxy-2-nitrobenzyl)ether, [3-alanine-carboxamide, or succinimidyl ester; 5-carboxyfluoresceinsuccinimidyl ester; 6-carboxyfluorescein succinimidyl ester;5-(6)- carboxyfluorescein succinimidyl ester; 5-(4,6-dichlorotriazinyl) amino fluorescein; 2 ', 7' -difluoro fluorescein; eosin-5-isothiocyanate; erythrosin5 -isothiocyanate; 6-(fluorescein-5- carboxamido) hexanoic acid or succinimidyl ester; 6-(fluorescein-5-(6)-carboxamido )hexanoic acid or succinimidylester; fluorescein-S-EX succinimidyl ester; fluorescein-5- isothiocyanate; fluorescein-6-isothiocyanate; Oregon Green® 488 carboxylic acid, or succinimidyl ester; Oregon Green® 488 isothiocyanate; Oregon Green® 488-X succinimidyl ester; Oregon Green® 500 carboxylic acid; Oregon Green® 500 carboxylic acid, succinimidylester or triethylammonium salt; Oregon Green® 514 carboxylic acid; Oregon Green® 14 carboxylic acid or succinimidyl ester; Rhodamine Green™ carboxylic acid, succinimidyl ester or hydrochloride; Rhodamine Green™ carboxylic acid, tn fluoroacetamide or succinimidylester; Rhodamine Green™-X succinimidyl ester or hydrochloride; RhodolGreen™ carboxylic acid, N, O-bis-(trifluoroacetyl) or succinimidylester; bis-(4-carboxypiperidinyl) sulfone rhodamine or di(succinimidylester); 5-(6)carboxynaphtho fluorescein, 5-(6)-carboxynaphthofluorescein succinimidyl ester; 5-carboxyrhodamine 6G hydrochloride; 6-carboxyrhodamine6Ghydrochloride, 5-carboxyrhodamine 6G succinimidyl ester; 6-carboxyrhodamine 6G succinimidyl ester; 5-(6)-carboxyrhodamine6G succinimidyl ester;5-carboxy-2',4',5',7'-tetrabromosulfonefluorescein succinimidyl esteror bis-(diisopropylethylammonium) salt; 5-carboxytetramethylrhodamine; 6-carboxytetramethylrhodamine; 5-(6)-carboxytetramethylrhodamine; 5-carboxytetramethylrhodamine succinimidyl ester; 6-Docket No. SLIN-032 / 01WO 217N-432617-WOcarboxytetrametliylrhodaminesuccinimidyl ester; 5-(6)-carboxytetrametliylrhodamine succinimidyl ester;6-carboxy-X-rhodamine; 5-carboxy-X-rhodamine succinimidyl ester; 6-carboxy-X-rhodamine succinimidyl ester; 5-(6)-carboxy-X-rhodaminesuccinimidyl ester; 5-carboxy-X-rhodamine triethylammonium salt; Lissamine™ rhodamine B sulfonyl chloride; malachite green; isothiocyanate; NANOGOLD® mono(sulfosuccinimidyl ester); QSY® 21 carboxylic acid or succinimidyl ester; QSY® 7 carboxylic acid or succinimidyl ester; Rhodamine Red™-X succinimidyl ester; 6-(tetramethylrhodamine-5-(6)-carboxamido) hexanoic acid; succinimidyl ester; tetramethylrhodamine-5-isothiocyanate;tetramethylrhodamine-6-isothiocyanate; tetramethylrhodamine-5-(and-6)- isothiocyanate; Texas Red® sulfonyl; Texas Red® sulfonyl chloride; Texas Red®-X STP ester or sodium salt; Texas Red®-X succinimidyl ester; Texas Red®-X succinimidyl ester; and X- rhodamine -5 -(6) isothiocyanate.

[0146] Other examples of fluorescent dyes for use with the particles described herein include, but are not limited to, BODIPY® dyes commercially available from Invitrogen, including, but not limited to BODIPY® FL; BODIPY® TMR STP ester; BODIPY® TR-X STP ester; BODIPY® 630 / 650-X STPester; BODIPY® 650 / 665-X STP ester; 6-dibromo-4,4-difluoro-5, 7 -dimethyl-4-bora-3a,4a-diaza-s-mdacene-3-propionic acid or succinimidyl ester; 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-3,5-dipropionic acid; 4,4- difhioro-5,7-dimethyl-4- bora-3a,4a-diaza-s-indacene-3-pentanoicacid; 4,4-difluoro-5,7-dimethyl-4-bora3a,4a-diaza-s-indacene-3-pentanoicacid or succinimidyl ester; 4,4-difluoro-5,7- dimethyl-4-bora-3a, 4a-diaza-s-indacene-3propionicacid; 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionicacid succinimidyl ester; 4, 4difluoro-5,7-dimefhyl-4-bora- 3a,4a-diaza-s-indacene-3propionic acid; sulfosuccinimidyl ester, or sodium salt; 6-((4,4- difluoro-5, 7-dimethyl-4- bora-3a,4a-diaza-s-indacene-3propionyl)amino) hexanoic acid; 6-((4,4-difluoro-5, 7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyI)amino) hexanoic acid or succinimidyl ester; N-( 4, 4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl) cysteic acid, succinimidyl ester, or triethylammonium salt; 6-4,4-difluoro-l,3-dimethyl-5-(4-methoxyphenyl)-4-bora-3a,4a-4,4-difluoro-5,7-diphenyI-4-bora-3a,4a-diaza-s-indacene-3-propionic acid; 4,4-difluoro-5,7-diphenyl-4-bora3a, 4a-diaza-s-indacene-3 -propionic acid, or succinimidyl ester; 4,4-difluoro-5-phenyl-4-bora-3a,4a-diaza-s-indacene-3-propionic acid, or succinimidyl ester; 6-((4,4-difluoro-5-phenyl-4-bora-3a,4a-diaza-s-indacene-3-propionyDamino) hexanoic acid or succinimidyl ester; 4,4-difluoro-5-(4-phenyl- l,3butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-propionicacid or succinimidyl ester; 4,4-difluoro-5-(2-pyrrolyl)-4-bora-3a,4a-diaza-s-indacene-3-propionic acid or succinimidyl ester;Docket No. SLIN-032 / 01WO 217N-432617-WO6-(((4,4-difluoro-5-(2-pyrrolyl)-4-bora-3a,4a-diaza-s-indacene-3-yl)styryloxy)acetyl)aminohexanoicacid or succinimidyl ester;4,4-difluoro-5-styryl-4-bora- 3 a, 4a-diaza-s-indacene-3 -propionic acid; 4, 4-difluoro-5-styryl-4-bora-3a,4a-diaza-s-indacene- 3-propionic acid or succinimidyl ester; 4,4-difluoro-l,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s- indacene-8-propionic acid; 4,4-difluoro-l,3,5,7-tetramethyl-4bora-3a,4a-diaza-s-indacene-8-propionic acid or succinimidyl ester; 4,4-difluoro-5-(2-thienyl)-4-bora-3a,4a-diaza-s-indacene-3-propionic acid or succinimidyl ester; 6-(((4-(4,4-difluoro-5-(2-thienyl)-4-bora- 3a,4a-diaza-s-indacene-3-yl)phenoxy)acetyl)amino)hexanoic acid or succinimidyl ester; and 6-(((4,4-difluoro-5-(2-thienyl)-4-bora-3a,4a-diaza-s-indacene-3-yl)styryloxy)acetyl) aminohexanoic acid or succinimidyl ester.

[0147] Fluorescent dyes for derivatization of the surface of one or more particles include, but are not limited to, Alexa Fluor® dyes commercially available from Invitrogen, including but not limited to Alexa Fluor® 350 carboxylic acid; Alexa Fluor® 430 carboxylic acid; Alexa Fluor® 488 carboxylic acid; Alexa Fluor® 532 carboxylic acid; Alexa Fluor® 546 carboxylic acid; Alexa Fluor® 555 carboxylic acid; Alexa Fluor® 568 carboxylic acid; Alexa Fluor® 594 carboxylic acid; Alexa Fluor® 633 carboxylic acid; Alexa Fluor® 647 carboxylic acid; Alexa Fluor® 660 carboxylic acid; and Alexa Fluor® 680 carboxylic acid. In some embodiments, fluorescent dyes for use with the particles and methods described herein include cyanine dyes commercially available from Amersham-Pharmacia Biotech, including, but not limited to Cy3 NHS ester; Cy5 NHS ester; Cy5.5 NHSester; and Cy7 NHS ester,

[0148] It is within the ordinary' skill in the art to select a suitable dye or dyes based on the desired spectral excitation and emission properties of the particle.

[0149] In some embodiments, particles are functionalized with one or more biomolecules, such as cell surface markers (see, e.g,, Tables 2-4), or fragments thereof, for example, extracellular portions thereof in the case of transmembrane proteins, for example, by attaching the one or more cell surface markers, extracellular portions or ligand binding regions thereof to the particle via a free amine, free carboxyl and / or free hydroxyl group present on the surface of the particle. Functionalization of a particle with a dye or cell surface molecule can also occur through a linker, for example a streptavidin / biotin conjugate.

[0150] Depending on the target cell, individual particles can be derivatized with one or more biomolecules, including cell surface markers, or fragments thereof, for example, extracellular portions thereof in the case of transmembrane proteins to further mimic the s truc tural properties to impart the synthetic particle with a desired biological function. Tables 3-4, provided below', set forth a non-limiting list of cell surface markers that can be used to derivative particles.Docket No. SLIN-032 / 01WO 217N-432617-WOAlthough the cell surface marker is provided, it is understood that a portion of the cell surface marker, for example, a receptor binding portion, a ligand binding portion, or an extracellular portion of tire marker can be used to derivative the particle (at the free functional group, as described above).Table 3. B cell maturation markers for use with the particles described hereinB-cell type Cell surface marker(s)Pro-B CD19, CD20, CD34, CD38, CD45RPre-B CD 19, CD20, CD38, CD45RImmature B CD 19, CD20, CD40, CD45R, IgMTr-B CD10, CD19, CD20, CD24, CD28Naive-B CD 19, CD20, CD23, CD40, CD 150 (SLAM), IgD, IgMB-l CD 19, CD20, CD27, IgMMemory B CD 19, CD20, CD28, CD40, IgA, IgGPlasma Cell CD9, CD28, CD31, CD38, CD40, CD95 (FAS), CD184 (CXCR4)Table 4. Cell surface markers for use with the particles described herein14-3-3 [alpha] [beta] Cdc-123 HPx214-3-3 [epsilon] Cdc-2 (p34) Hrk14-3-3 [zeta] Cdc-25A Phosph (Serl7) Hsc7014-3-3 [theta] Cdc-25C HSD17B114-3-3 [sigma] Cdc-37 HSD3B115 -Lipoxygenase 1 Cdc-45L HSF1160 kD NeurofilamentCdc-6Medium HSF2200 kD NeurofilamentHeavy CDc-7 HSF42H2 Cdkl HSL3G11 sialoganglioside Cdk2 Hspl05antigen4E-BP1 Cdk4 Hspl44E-BP1 Phospho Cdk5 Hsp22(Tlir37 / 46)5 -Methylcytidine Cdk6 HSP255HT3A receptor Cdk7 Hsp275T4 Cdk9 Hsp4068kDa Neurofilament CdkAl Hsp47Light7.1 CdkN2A Hsp60Docket No. SLIN-032 / 01WO 217N-432617-WO70 kD Neurofilament Light CdkN3 Hsp70A20 CDT1 Hsp70-2A2B5 CDX2 Hsp90AAK1 CEACAM19 Hsp90[alpha]ABCA1 CF. ACAM20 Hsp90[beta]ABCA7 CEACAM7 HspA4ABCB4 CEBP[alpha] HspA6ABCB5 CEBP[beta] HSPA9ABCC10 CEND1 HspB2ABCC11 (TN PA HspB7ABCG1 CENPE HSVtagABI2 CENPF HTLV I gp46ABIN3 CENPH HTLVI pl9ABIN3[beta] Centrin 2 HtrA2 / OniiABL2 CFAH Human Papillomavirus 16 (E7) Abraxas cFos HuntingtinACAA1 CFTR HUS1ACADM CGB5 Hydrogen Potassium ATPase [beta] ACAT2 cGKl I-Ak (A[alpha]k)ACBD3 CH2 I-Ak (A[beta]k)ACD CHCHD5 la (B cells)ACE2 CHD3 IBA1Acetyl Coenzyme ACHD4 IBP2CarboxylaseAcetyl Coenzy me A Chemerin ICADCarboxylase [alpha]Acetyl Coenzyme ACHIPS, C-terminus IDOSynthetaseAcetylated Lysine CHIPS, N-terminus IFABPAChRfalpha] Clikl IFN-[alpha]AChR[beta] Chk2 IFN-[alpha]lAChR[gamma] Chondroitin Sulfate IFN- [alpha] 2 [beta] Aconitase2 CHOP IFN-[beta]ACOT12 Chromogranin C IFN-[gammajACSA2 ChTl IFN-[gamma]R[beta]ACSF2 chTOG IFN-I©ACSM5 cl API IFNA1Act! C1AP2 IFN ARIActivation molecule 8 (BCIAS1 IFT88cells)Activin A Receptor TypeCIDEA IB IgActivin A Receptor TypeCIP4IIB Ig (polyspecific)ACTN3 CISDI Ig light chain 1°ACY1 CITED 1 Ig light chain I»ACY3 CITED2 Ig light chain I»l, I»2, 1»3Docket No. SLIN-032 / 01WO 217N-432617-WOADA eJun IgAADAMI 2 eJun Phospho (Tyr91 / Tyr93) IgA (Fab2)ADE2 CKII[alpha] IgA (H)Adenosine Al Receptor CKMT2 IgA. i°Adenosine A2aR CLASP 1 igA, i»Adenovirus Clathrin IgAlAdenovirus Fiber Claudin-1 IgA2monomer and trimerAdenovirus hexon protein CIaudin-10 IgDAdenylate Kinase 1 Claudin-15 IgD ([delta] heavy chain) Adenylosuccinate Lyase Claudin-16 IgDaADFP Claudin-18 (C-tenn) IgDbADH1B Claudin-18 (Mid) IgEADH6 Claudin-4 IgE, FADH7 Claudin-5 IgEaADI1 Claudin-6 IgEbAdiponectin CLAW-H IgGAdiponectin Receptor 2 CLEC12A IgG (Fab H / L)Adipose Triglyceride CLEC1B IgG (Fab)LipaseADP Ribosylation Factor CLEC4A IgG (Fab2 Fc)ADP-ribosyltransferase 2.2 CLEC4M IgG (Fab2 H / L)geneAdrenodoxin CLEC9A IgG (Fab2)AF10 CLIP IgG (Fc)AFAP1 CLOCK IgG (H / L)Clostridium botulinum ToxinAFP IgG ([gamma] chain specific)B AG2 CLPP IgG FdAGAP1 cMaf IgG light chainAGPAT5 cMet IgG, FAGR2 CMKLR 1 IgG / IgMAHSG CMRF44 IgG / IgM / IgAAICDA CMRF56 IgG / IgM / IgA (Fab2 H / L) AID cMyb IgG / IgM / IgA (Fab2)AIF cMyc IgG / IgM / IgA (H / L)AIM-2 CNDP2 IgG / IgYAiolos CNTFRfalpha] IgGlAIPL1 COASY IgGl (heavy chain)AIRE Coatomer [delta] IgGl, 1°AK3 Cofilin IgGl. I»AK3L1 Colecl2 IgGl / 2aAK5 Collagen I IgG 1 / 3Akt Collagen I / III IgG laAkt (pS473) Collagen II IgGlbAkt (pT308) Collagen III IgG2Docket No. SLIN-032 / 01WO 217N-432617-WOAktl Collagen IV IgG2, FAkt2 Collagen V IgG2, 1»Akt3 Collagen VI IgG2 / 3Albumin Collagen VII IgG2aAlcohol Dehydrogenase COMMDI IgG2a, FAldehyde Reductase Complement Factor B IgG2a, t»ALDH1A1 Complex I Inimunocapture IgG2a / bConjugated Choline GlutaricALDH1L1 IgG2bacidALDH2 Connexin 26 IgG2b, 1°ALDH3A1 Connexin 30 IgG2cALDH3A2 Connexin 30.2 IgG2c, 1°ALDH5A1 Connexin 30.3 IgG3ALDH6A1 Connexin 32 IgG3. FALDH7A1 Connexin 36 IgG3, 1»ALDOB Connexin 37 IgG4Aldolase B Connexin 37 (C-term) IgGDaAlexa Fluor® 405 / CascadeConnexin 37 (Mid) IgKBlueAlexa Fluor® 488 Connexin 39 IGKCALG2 Connexin 39 (Mid) IgLAlix Connexin 40 (C-term) IGLC2Allerginl Connexin 40 (Mid) IgMalpha 1 Antitrypsin Connexin 43 IgM (Fab2)alpha 1 Catenin Connexin 45 IgM (Fc)alpha 1 Sodium PotassiumConnexin 45 (C-term) IgM (HZL)ATPasealpha 2 Catenin Connexin 46 IgM, Falpha 2 Macroglobulin Connexin 47 IgM, i»alpha Actin 1 Connexin 57 (C-term) IgMaalpha Actin 2 Connexin 57 (Mid) IgMbalpha Actinin Contactin 2 IgYalpha Actinin 2 COPS3 Iga€™salpha Actinin 3 Coronavirus Ihhalpha Actinin 4 Coronin 1A Ikarosalpha Adaptin Coronin IB IkB [alpha]alpha Adducin Cortactin IkB [beta]alpha B Crystallin Cortical Thymocytes IkB [zeta]alpha Fodrin COX I IKK[alpha]alpha Internexin COX I / III IKK [beta]alpha Synuclein COX II IKKfgamnia] p(S376)ALS1 COX IV IKK [epsilon]AMACR COX VA IL-10Aminopeptidase P COX VIA1 IL-IIR[alpha]Coxsackie AdenovirusAML1 IL-12ReceptorDocket No. SLIN-032 / 01WO 217N-432617-WOAmphiphysin CPF IL-12 (p35)AMPK [alpha] CPI17[alpha] IL-12 (p70)AMPK[alpha]l CpnlO IL-12 R[beta]l AMPK[alpha]2 CPO IL-12 R[beta]2AMPK [beta] 1 CPS1 IL-12 / IL-23 (p40) AMPKfgamma] 1 CPT2 IL-13Amyloidfbeta] 42 CRABP1 IL-15ANAPC2 CRABP2 IL-15 / IL-15RANDI CRALBP IL-15R[alpha]Androgen Receptor Creatine Kinase BB IL-16Angiotensin I Creatine Kinase MM IL-17DAngiotensin II Receptor 2 CREB IL- 17 AAngiotensin III CREB Phospho (Serl33) IL-17A / FANKRD53 cRel IL-17BAnnexin IV Criptol IL-17CAnnexin V CRISP3 IL-17EANP Crk p'S IL-17FAnti-Kudoa tiny sites CrkL IL-18Anti-T. brucei procvclinCrkL (pY207)(GPEET) IL-18BPAnti-T. brucei procyclinCROT IL-19(phosphorylated GPEET)Antiglobulin (Coombs) CRRY IL- IRAAntithrombin III CRTAM IL-1RNAP2 [alpha] CRTC3 IL- 1 [alpha]AP2 [alpha] [beta] CRY2 IL-l[beta]AP2 [gamma] Cryptochronie I II.-2AP2M1 Cryptosporidium IL-20R2AP2S1 Cryptosporidium Parvum IL-20R[alpha]APAF1 CRYZL1 IL-20R[beta]APBB3 CSK IL -21ARC CSK Binding Protein IL-22APC-1 CSPS IL-22R[alpha]2APC-10 cSrc IL -23 (p!9)APC-11 CST2 IL-23RAPC-2 CTDSP1 IL-24APC-3 CTNNA3 IL-25APC-5 CTNNBLI IL-27APC-7 Cullin I IL -27 (p28)APC-8 Cullin 2 IL-27R[alpha]APE1 Cullin 3 IL-28APG12 Cullin 4A IL-28R[alpha]APG3 Cullin 4A / B IL-29APG5 Cullin 4B IL-3Cutaneous LymphocyteAPG7 IL-31AntigenDocket No. SLIN-032 / 01WO 217N-432617-WOAPMAP CUTL1 IL-32 [alpha] [beta] [gamma] [delta] Apo -2.7 CX3CL1 IL-32 [alpha] [beta] [delta] Apo-2.7 (7A6) CX3CR1 IL -33ApoE CXCL1 IL-34ApoE4 CXCLIO IL-4APOER2 CXCL12[a1pha] IL-4R [alpha]Apolipoprotein Al CXCL12[beta] IL-5Apolipoprotein All CXCL13 IL -6Apolipoprotein AIV CXCL9 IL-7Apolipoprotein B CXCR7 IL-7R[alpha]Apolipoprotein CIII CXorf26 IL-8Apolipoprotein D Cyanine IL-9Apolipoprotein E CYB5R2 ILF3Apolipoprotein F CYB5R3 U. KApolipoprotein H Cyclin A ILK1Apolipoprotein J Cyclin A2 ImmunofluorescenceN-[gamma] Apolipoprotein LI Cyclin Bl IMP3Apolipoprotein M Cyclin B2 Importin9Apoptotic neutrophils Cyclin DI Influenza A Virus M2 Protein APP Cyclin D2 Influenza B Vims Nucleoprotein Aquaporin 1 Cyclin D3 ING1Aquaporin 5 Cyclin E ING2ARF1 Cyclin E2 ING3ARF5 Cyclin H ING4ARFGAP1 Cyclins D1 / D2 / D3 Inhibin [alpha]ARFRP1 Cyclophilin 40 iNOSArgonaute-1 CYLD INPP4AARH CysLTl INPP4BARHGAP25 Cy statin C InsulinARHGAP4 Cystatin S Insulin Degrading Enzyme (IDE) ARE 11 Cytochrome B245 heavy Insulin Receptor RchainARL5B Cytochrome B245 light chain Integrin [alpha]4 / [beta]7 ARPC5 Cytochrome c Integrin [alpha] 9 / [beta]l Artemis Cytochrome P450 17A1 Integrin [alpha]V / [beta]5Ar, 1 bydrocatbon Receptor Cytochrome P450 19A1 Integrin [alpba]V / [beta]6 ASB-1 Cytochrome P450 1A2 Integrin [beta] I Phospho (Tyr783) ASCC1 Cytochrome P4502A6 Integrin [beta]l Phospho (Tyr795) ASCC2 Cytochrome P4502B6 Integrin [beta] 5ASGPR Cytochrome P4502C9 Integrin [beta]6Asialo-GMl Cytochrome P4502J2 Integrin [beta]7ASK1 Cytochrome P4503A4 Intercalated DNAAsparagine synthetase Cytochrome P4503A5 Intra Acrosomal Protein Ataxin 1 Cytochrome P450 Reductase Intra-Acrosomal ProteinsATF1 Cytokeratin Invariant NK TDocket No. SLIN-032 / 01WO 217N-432617-WOATF2 Cytokeratin (acidic) IP10ATG4A Cytokeratin (basic) IQGA1ATG9A Cytokeratin (Pan-reactive) IRAKIATIC Cytokeratin 1 IRMOAtlantic Salmon Ig Cytokeratin 10 IRAK4ATM Cytokeratin 10 / 13 IRE1ATP citrate lyase Cytokeratin 13 IRF1ATPIB3 Cytokeratin 14 IRINATP5A Cytokeratin 14 / 15 / 16 / 19 IRF4ATP5H Cytokeratin 15 IRF5ATP5. T Cytokeratin 16 IRF6AIP5O Cytokeratin 17 IRINATP6V0D1 Cytokeratin 18 IRF7 (pS477 / pS479) ATP6V1B1 Cytokeratin 19 IRF8ATPB Cytokeratin 2 IRF9ATRIP Cytokeratin 20 IRS1Aurora A Cytokeratin 4 IRS1 (pY896)Aurora A Phospho Cytokeratin 4 / 5 / 6 / 8 / 10 / 13 / 18 IRS2(Thr288)Aurora B Cytokeratin 40 IRS4Aurora B PhosphoCytokeratin 5 ISG15(Thr232)AVEN Cytokeratin 5 / 6 / 18 ISG20Avian Influenza A Cytokeratin 5 / 8 ISL1NeuraminidaseAvidin Cytokeratin 6 IsthrninlAxin 2 Cytokeratin 6a ITCHAxl Cytokeratin 7 Integrin [alpha] 7B and Activated T Cells Cytokeratin 7 / 17 ITKB Cell Cytokeratin 8 ITPR1B Cell Subset Cytokeratin 8 / 18 / 19 Jagged2B cells (pan reactive) D4-GDI JAK2B lymphocytes antibodyDAB2 JAK3[UCH-B1]b-Endorphin DACH1 JAM2B-Raf Phospho JAMI.(Thr598 / Ser601) DAND5B18R DAP1 Japanese encephalitis virus NS1 glycoproteinB7-H4 DAPI2 INKBACE1 DAPK1 INK Phospho (ThiT83 / Tyrl85) BACE2 DAPK2 JNK1 / JNK2 / JNK3BACH1 DARPP32 JNK2baculovirus envelope gp64 Daxx Junctional Adhesion Molecule C proteinBAG1 DAZL Junctophilin-1 (C-temi)BAG2 DBC1 Junctophilin-1 (Mid)Docket No. SLIN-032 / 01WO 217N-432617-WOBAG3 DCAMKL1 Junctophilin-2 (C-term)B AG4 DCC Junctophilin-3 (C-term) BAIAP2 DCIR2 KAP1BAK DCLRE1B KATNA1BAMBI DCPla KCNH1BAP31 DcR3 KDELBAP37 DCTN2 KDM4Dbasal cell Cytokeratin DcTRAlL-Rl Ki-67Basophils DcTRAIL-R2 KIF22Bassoon DCXR KIF3ABATF DDB1 K1F4ABax DDDDK tag KIFA3BCAR1 DDX3 Kindlin2BCAR2 DDX4 Kinetoplastid Membrane Protein 11(KMP-1))BCKD complex E2 subunit DDX50 KIR-2.1Bcl-10 DECR1 K1R-2D (pan CD158)Bcl-2 D ectin 1 KLF4Bcl-2 (pS70) Dectin2 KLF6Bcl-2 like 12 DEF8 KLHBcl-2 like 2 Defensin [alpha] 1 KLHL11Bcl-22 DELETE KLRA3Bcl-2 Al delta 1 Catenin KLRC1Bcl-2 [alpha] Delta like protein 1 KLRG1Bcl-3 Delta like protein 4 KMT4Bcl-6 Delta Opioid Receptor KMT5ABcl-xL DeltaC KOR-SA3544Bcl-XS / L DeltaD KS1 / 4BCR Dendritic Cell Marker Ksp37BCSC1 Deoxycytidine kinase KSR1BDH2 Desmin Ku70BDKRB2 Desmoglein 2 Ku70 / 80BDNF Desmogleinl Ku80Beclinl Desmoplakin Kudoa ThyrsitesBestrophin 3 Destrin Kunitz Protease Inhibitor beta 2 Adrenoreceptor Dextran Kv4.2Beta 3 AdrenergicDGKAReceptor L / S-MAGbeta 3 Sodium PotassiumDicer Labeling Check Reagent ATPasebeta Actin DISCI (C-term) Lactate Dehydrogenase beta Arrestin 1 DISCI (Mid) Lactate Dehydrogenase B beta Arrestin 2 Dishevelled 3 Lambdabeta Catenin Disialoganglioside GD2 Lamin Abeta Catenin (npaa 27-37) Disialoganglioside GD3 Lamin A / Cbeta Catenin (npaa 35-50) Dkkl Lamin B ReceptorDocket No. SLIN-032 / 01WO 217N-432617-WObeta Catenin (pS45) Dkk3 Lamin B 1beta Dystroglycan DLC8 Lamin B2beta galactosidase DLK1 Lamin Cbeta galactosidase fusion Dlx5 Lamininproteinsbeta Synuclein DM-GRASP Laminin 5beta2 Microglobulin DMT1 Laminin ReceptorBHMT DNA-PKcs Laminin [beta] 1DNA-PKcs PhosphoBid(Thr2609) LAMP2aBiglycan DNAI1 LAMP2bBilirubin Oxidase DNAJA2 LATBim DNAJB2 LAT (pY171)BiinL DNAJC3 LAT (pY226)BINI DNAPK LBP BIND DNM1L LCDBiotin Dnmtl LC3BBiP Dnmt3b LCATBLBP DNP LekBlimp- 1 D0K2 Lek (pY505)BLK D0K7 LDH1BLNK Dopamine Receptor DI LDH1 / B / CBLNK (pY84) Dopamine Receptor D3 LDL (NIDA oxidized)Blood Group A Antigen Dopamine Receptor D5 LDLRBlood Group AB Antigen Dopamine [beta] Hydroxylase LEFTBlood Group B Antigen Doublecortin Leishmania LPG (repeat epitope)Leislimania Major Surface Protease Blood Group H ab Antigen DPI(GP-63)Blood Group H abDPH2 LEKTIAntigen / n AntigenBlood Group II inhibitor DPP10 Leukemia Inhibitoiy Factor Blood Group Lewis a DPP3 Leukotriene A4 hydrolase Blood Group M Antigen DPP9 Leukotriene B4 Receptor Blood Group N Antigen Dppa4 LHX3Blooms Syndrome Protein DPYD Ll-CadherinBimBM1 DR3 LIFBMAL1 DRAK1 DNA Ligase IBMI1 DRAK2 DNA Ligase IIIBink Drebrin LIM kinase 2BMP 15 DTYMK LIME1BMP4 DUSP23 LINIK 1BMP7 DUSP27 LIMSIBMPR1A DUSP3 Lin28BMPR2 DUSP5 Lineage CocktailBMX DUSP6 Lipin 1Docket No. SLIN-032 / 01WO 217N-432617-WObMyc DUX4 LISIBNIP2 DYKDDDDK Epitope Tag Liver Carboxylesterase 1 BNIP3 Dynamin LKB1BNIP3L Dynaminl LM02BOB1 Dynaniitin LOXBORA Dynein light chain 2 LOX IBorealin Dysbindin LRP5 / 6Borrelia burgdorferi Dysferlin LRP6BPI Dystrobrevin [alpha] LRPAP1BRaf Dystrobrevin [beta] ESDIDystroglycan PhosphoBRCA1(Tyr893) LSP1BRCC36 E. Coli O / E LSSBRD3 E2A-Pbxl LT[alpha]BrdU E2F1 LuciferaseBRF1 E47 LXR[alpha]BRG1 E4BP4 Ly-108BRN3A Ea52-68 peptide bound to I-A Ly-49ABtk Ea52-68 peptide bound to the Ly-49A / D1-ABtk(pY551) / Itk(pY511) EAAT1 Ly-49AB6BTLN-2 Early B Lineage Ly-49C / F / I / HBTN1A1 EBF1 Ly-49C / 1Bui EBI3 Ly-49DBula EBP50 Ly-49E / FBula / Bulb ECGF1 Ly-49FBulb ECHI Ly-49GBubRl ECRG4 Ly-49G2Bulb EDA Ly-49G2B6 Butyiylcholinesterase EDA-A2R Ly-49HC peptide EDG1 Ly-49IC reactive protein EDG2 Ly-51C / EBP[beta] EDG3 Ly-6A.2 / Ly-6E.1Cl Inhibitor EDG6 Ly-6A / EC15orf40 EEA1 Ly-6bC16orf72 EEF1G Ly-6B,2Clorf50 EEF2 Ly-6CC1Q EEF2K Ly-6DC1QA EEN Ly-6GCl QB EFEMP 1 Ly-6G / CC1QC EFEMP2 Ly-6KC1QG Eg5 Ly-77Clr Eg5 Phospho (Thr927) Lymphotoxin [beta]Cis EGF Lymphotoxin [beta] ReceptorC20orf30 EGF Receptor LynDocket No. SLIN-032 / 01WO 217N-432617-WOC20orf43 EGF Receptor (pY1173) LYRICC21orf56 EGF Receptor (pY845) Lysophospholipase 1 C21orf59 EGF Receptor (pY992) Lysosomal acid lipaseC2orf43 EGR1 LysozomeC3 EGR2 LysozymeC3aR EHD1 Ly ve 1C3b elFl M-CSFM13 Bacteriophage Coat Protein C3c eIF2C2g8pC3d EIF2S 1 Ml 3 Bacteriophage Protein C4 eIF2 [gamma] MAAC4 binding protein eIF3 Mac-2BPC4b eIF3D macroH2 A.1C4c eIF3D (p66) MacrophageC4d eIF3F Macrophage Activator C4orf42 eIF3G Macrophage galactose lectin C5 eIF3H (p40) Macrophage / Granulocy te C5aRl eIF3I (p36) Macrophages / Monocytes ( 51.2 eIF3J MAD2C6 eIF3K MadCAMlC6orf64 eIF4B MADDC8AZB / G eiF4E MADH7C9 eIF4E (pS209) MAFBC9orf41 eIF4E2 MAGCA125 eIF5A MAGE-ACA19.9 eIF6 MAGE1CAB39 Elastase MAIR2CACNA1S Elkl MAIR4CACNA2 Elkl (pS383) MALT1CACNG1 ELK3 Mammaglobin ACAD Elongin B MAP1LC3ACadberin 1 Elongin C MAP2Cadherin 10 EMAP II MAP2BCadherin 11 Embigin MAP2K1IP1Cadherin 7 EMG1 MAP3K8Cadherin 8 Emil MAP4 Phospho (Ser768) Cadherin 9 EMR3 MAP4K1Cadherin E EMSY MAP4K4Cadherin II Ena / Vasp-like MAPK12Cadberin K EndoG MAPK6Cadherin P EndoGlyx-1 MAPKAP Kinase 2Cadherin R Endomucin MAPKAP Kinase 2 Phospho (Thr334)CAK C Terminus Endothelial Cells MARCKSCAK N Terminus Endothelial Lipase MARCODocket No. SLIN-032 / 01WO 217N-432617-WOCAK PhosphoEndothelial Venule Marker Marginal Zone B Cells(Seri 64 / Thr 170)Calbindin Endothelium MARK2Calcineurin A Engrailed 1 MARK3Calcitonin Receptor EN01 MARTICalcium Sensing Receptor Enolase 1 Mast CellCaldesmon eNOS Mast Cell Protease 11 Calgranulin A eNOS (pS1177) mature macrophage marker Calgrannlin B Entpd2 MBD1Calmodulin Eonies MBD2Calnexin - ER membraneMBLmarker EosCalpain 1 Epacl MCL1Calpain 2 Eph Receptor Al MCM2Calpain 9 Eph Receptor A2 MCM3Calpain SI (small subunit) Eph Receptor A4 MCM4Calpastatin Eph Receptor B4 MCM5Calponin Eph Receptor B6 MCM6Calreticulin Ephrin A2 MCM7Calre tinin Ephrin A3 MCP-1Calsequestrin 2 EPHX2 MCP-4CaMKJ EPM2AIP1 MCP-8CaMKII EPOR MCSFCaMKII Phospho (Thr286) EPS15R MD1CaMKII[delta] Epsin 1 MD2CamKIV Epsin 2 MDCCaMKI [alpha] ER-HR3 MECT1CAMLG ER-MP54 MEF2AcAMP Protein KinaseER-TR7 MEIS1Catalytic subunitc AMP Protein KinaseER81 MEK1Catalytic subunit [alpha]Cannabinoid Receptor I ERAB MEK1 (p298)Cannabinoid Receptor 11 ERCC1 MEK1 (pS218) / MEK2 (pS222) CAP-G2 ERG MEK1 / 2 (pS222)CAP 18 ERK1 MEK2CAP2 ERK1 / 2 (pT185 / pY187) MEK3CAP3 ERK1 / 2 (pT202 / pY204) MEK4Carbonic Anhydrase I ERK1 / ERK2 MEK5Carbonic Anhydrase IX ERK2 MEK6Caiboxylesterase 1 ERK5 MEK7Carboxypeptidase Al ERMAP MEKK1Carboxypeptidase A2 ERp29 MEKK2CARD 11 ERp72 MEKK3CARD8 Erythroid Cells MEKK4CARD9 Erzin / Radixin / Moesin MelanomaDocket No. SLIN-032 / 01WO 217N-432617-WOCardiac Troponin T ER[alpba] Phospho (Serl67) MELKCARKL ESAM MEM01Estrogen Inducible ProteinCARMI MenapS2Casein Kinase 1 [alpha] Estrogen Receptor MeninCasein Kinase 1 [gamma]2 Estrogen Receptor [alpha] ME0X2Casein Kinase 2 [beta] Estrogen Receptor [beta] MerlinEstrogen Related ReceptorCaspase 1 MERTKalphaCaspase 10 ETAR MesothelinCaspase 11 Ethenoadenosine MetallothioneinCaspase 12 ETS1 MetRSCaspase 2 EVKA mGluR5Caspase 2L EVI2B MGMTCaspase 3 EWSR1 MHC Class ICaspase 4 EXD1 MHC Class I (H-2Db) Caspase 5 EXOSC3 MHC Class I (H-2Dd) Caspase 6 EXOSC7 MHC Class I (H-2Dk) Caspase 7 EYA2 MHC Class I (H-2Dq / Lq) Caspase 8 EZH1 / 2 MHC Class I (H-2Kb) Caspase 9 Ezrin MHC Class I (H-2Kb / Db) Catalase Ezrin (pY353) MHC Class I (H-2Kb / Dd) Catechol -0- F-actin MHC Class I (H-2Kd a3 domain) niethyltransferaseCathepsin D F10A1 MHC Class I (H-2Kd) Cathepsin K F4 / 80 MHC Class I (H-2Kd / Dd) Cathepsin L FAA4 MHC Class I (H-2Kd / Dd / q / u / v) Caveolinl FABP4 MHC Class I (H-2Kk) Caveolinl (pY14) Factor I MHC Class I (H-2Kq) Caveolin2 Factor IX MHC Class I (H-2Ks)Cbl Factor VIII. vWF (delete) MHC Class I (H-2Ld)CBP Factor XHIa MHC Class I (H-2Ld / Db) CBWD1 FADD MHC Class lb (H2-M3) CBX1 FAHD2A MHC Class IIcCbl (pY700) FAK MHC Class II (DQ)cCbl (pY774) FAK (pS910) MHC Class II (DR)CCDC98 FAM119A MHC Class II (I-A)CCK4 F AMI 75 A MHC Class II (I-A / E) CCL11 FAM84B MHC Class II (I-Ab)CCL17 FAM91A1 MHC Class II (I-Ab / Ad) CCL18 FANCC MHC Class II (I-Ab / As) CCL19-Fc FANCD2 MHC Class II (I-Ad)Fanconi anemia D2 PhosphoCCL20 MHC Class II (I-Ak)(Ser222)CCL21 FAP MHC Class II (I-Ak / Ad / Ab / Aq / Ar)CCL25 Fascin MHC Class II (I-Ak / As)Docket No. SLIN-032 / 01WO 217N-432617-WOCCL3 FBP1 MHC Class II (I-Ap)CCL5 FBXO21 MHC Class II (I-Aq)CCL6 FBXO31 MHC Class II (I-E) CCNB1IP1 FBXO42 MHC Class II (I-Ei0)CCR10 FBXO43 MHC Class II (RT1B)CCRH Fc Receptor Binding Inhibitor MHC Class II (RTIBu) CCRD6 Fc receptor IgA+IgM MHC Class II (RT1D) CCRL2 FcR MHC Class II [beta]GDI FcRL6 MHC QalbCD 1.1 FcRLA MICACD 10 Fc[epsilon]RI MICA / MICBCD 100 FDC MICECD 101 FDFT1 Microfold (M) CellsCD 102 FDPS Microtubule Associated Protein 2ab CD 103 FE65 Microtubule Associated Protein RP / EB 2CD 104 FeLVp27 MidkineCD 105 FEN1 Mineralocorticoid Receptor CD 106 FER MIP-l[beta]CD 107a Ferritin Heavy Chain MIPEPCD 107b Ferritin Light Chain MitochondriaCD108 Ferritin, mitochondrial MitofilinCD 109 FES Mitofusin 1CD 11 Fetal Hemoglobin Mitofusin 2CD 110 FGF acidic Mitotic CellsGDI 11 FGF basic MKK6CD112 FGF21 MLH1CD 113 FGFR1 MLK3CD 114 FGFR2 MLL1CD115 FGR MLLT11GDI 16 FH MMP1CD117 FHLl MMP10CD 118 Fibrillarin MMP11CD119 Fibrillin MMP12CD Ila Fibrinogen MMP13CD! la, strain Fibrinogen [alpha] chain MMP14polymorphismCDlla / CD18 Fibrinogen [gamma] chain MMP15CD 11b Fibrinopeptide A MMP17CDllb / c Fibrinopeptide B MMP19Fibroblast activation proteinCD 11c MMP2[alpha]CD lid Fibroblast Surface Protein MMP20CD 120a Fibroblasts / Epithelial cells MMP21CD 120b Fibronectin MMP26CD121a Fibronectin Receptor MMP3Docket No. SLIN-032 / 01WO 217N-432617-WOCD12lb Fibulin5 MMP8CD 122 Ficolin B MMP9CD 123 Filaggrin MnklCD 124 Filamin A niNOSCD 125 FITC MnSODCD 126 FITC / Oregon Green MoesinCD 127 F1V Monoamine Oxidase BCD 129 FIV gpl20 Monocyte / GranulocyteCD 13 FIV gp95 Mononuclear Phagocyte Mouse Embiyonic Fibroblast (mEF) CD 130 FIVp24Feeder CellsCD131 FIV p24 gag Mouse LineageCD132 FKBP12 MPP1CD 133 FKBP4 MRCL3CD 133 / 2 FKBP6 MRE11CD134 FKBPL MRGPR-X2CD135 FLiC MRI1CD136 Flightless 1 MRP14CD 137 FLIP MRP2CD137L Flt3L MRP3CD138 Fluorescent Protein MRP4CD139 FLV gp70 MRP5CD 14 FLYWCH2 MRP6CD 140a FMC7 MRP8CD 140b fMLP Receptor MRP8 / 14CD 140b (pY1009) FMRP MSC (W8B2)CD 140b (pY1021) FNTA MSC (W3D5)CD 140b (pY771) FNTB MSC (W5C5)CD140b (pY857) Follicular Dendritic Cells MSC (W7C6)CD 141 Fos MSC / NPCCD 142 FOXA1 MSH2CD 143 FOXA2 MSH6CD 144 FOXC2 MSI2HCD 146 FOXD3 MSK1CD 147 FOXI1 MST1CD 148 FOXJ1 MST1 / MST2CD 15 FOXM1 MST3CD 150 FOXO1 MST4CD151 FOXO3A MST4 / MST3 / STK25CD 152 FOXP1 mTORCD 153 FOXP3 Muc-16CD 154 FPRL1 Muc-2CD155 FR4 Muc-3CD 156c Fra2 Muc-4CD 157 Fragilis Muc-7Docket No. SLIN-032 / 01WO 217N-432617-WOCD 158a FRAT1 MULT-1CD158a / h Frataxin Muncl3-4CD158b Frequenin Muncl8CD158bl / b2 / j Frizzled- 1 MUPP1CD158d FSH [alpha] Mus81CD158e FSH[beta] Musashi 1CD158e / k Muscarinic Acetylcholine Receptor FUK 2CD158el FUS muscle ActinCD158el / e2 FXYD3 Muscleblind-like 1CD158f FYB MVPCD158g Fyn MYBBP1ACD15811 Fyn (pY528) / c-Src (pY530) MYBPC3CD158i Fyn-Related Kinase Myc tagCD 158j FZR1 MyD88CD159a G-CSF Myelin Basic ProteinMy elin oligodendrocyte CD159c G3BPglycoproteinCD 15s G6PD Myelin PLPCD 16 GABI Myeloid AntigenMy eloid Cell NuclearCD 16 / 32 GAB2Differentiation AntigenCD 16 / 56 GABA B Receptor 2 Myeloid LineageCD 160 GAB ARAP MyocilinCD 161 GAD65 MyogeninCD161a GAD67 Myosin heavy chainCD 162 GADD34 Myosin ILACD162R Galacto-cerebroside Myosin light chain 2CD 163 Galactocerebroside Myosin light chain 3CD 164 Galectin 1 Myosin light chain kinaseCD 165 Galectin 10 My osin PhosphataseCD 166 Galectin 3 Myosin Phosphatase 1 / 2CD 167a Galectin 4 MYST2CD 168 Galectin 7 NADH2CD169 Galectin 8 NaflCD 16b Galectin 9 NAKCD 17 gamma Svnuclein NanogCD 170 Ganglioside GD2 NAPE-PLDCD 171 Ganglioside GD3 NATlCD 172 Ganglioside GM1 Native Lipoteichoic AcidCD 172a Gankyrin Natriuretic Peptide Receptor A CD172a / b GAP Natural Killer CellNatural Killer Cell Activation CD 172 b GAP43StructuresCD 172g GAPDH NBS1CD 173 GARP NC1.1Docket No. SLIN-032 / 01WO 217N-432617-WOCD 177 GAS2 NCF4CD 178 GAS7 NekCD 178.1 GAT2 NCOA1CD 179a GATA1 NCOA2CD 179b GATA2 NCX1CD 18 GATA3 NDUFAF1CD 180 GATA4 NDUFB4CD181 GATM NDUFS3CD 182 GBA3 NEDD8CD 183 GBE1 NEK2CD 184 GBP1 NEK6CD 185 GBP2 NEK7CD 186 GBP5 NEK9CD 19 GC1qR NEK9 Phospho (Thr210)CD 191 GCDFP15 NestinCD 192 GCDH NETO2CD 193 GCK1 Neurabin1CD 194 GCLM Neuregulin1CD 195 GCN2 Neuregulin3CD 195 (cytoplasmic) GCN5 NeuroblastomaCD 195 Phospho (Ser337) GCTM2 NeuroD1CD195 Phospho (Ser349) GDAP1L1 NeuroD2CD 196 GDF15 Neurofib ro minCD 197 Gelsolin Neurofilament Heavy Protein CD 198 Gemini Neurofilament Medium Protein CD 199 Gephyrin Neurogenin 2CD la GFAP Neurokinin 1 ReceptorCD lb GFP Neuron Specific Enolase CDlb / c GILZ Neuronal Growth Factor Receptor CDlc GIMAP4 Neurotensin Receptor 1CD Id GIPR NFkB p50 / p105CD Id [alphaJGalCerGIT2Complex NFkB p65 (pS536)CD2 GITRL NFATclCD20 GLAST NFkB p50CD200 Glil NFkB p50 / p105CD200R Glial Fibrilary Acidic Protein NFkB p52 / p100CD200R3 Glicentin NFkB p65CD201 GLIPR1L1 NFkB p65 (pS529)CD202b Glucagon NG2CD203a Glucocorticoid Receptor NGFCD203c Glucocorticoid Receptor alpha Nhedc2CD204 Glucose 1 Dehydrogenase NHERF1CD205 Glucose 6 Phosphate NicastrinIsomeraseDocket No. SLIN-032 / 01WO 217N-432617-WOCD206 GLUH1 NineinCD207 GLUT1 NitrotyrosineCD208 GLUT2 NKG2A / C / ECD209 GLUT4 NKG2AB6CD209b GLUT5 NKp80CD21 Glutamate receptor 2 NKX3. ICD21 / CD35 Glutamate receptor 2 / 3 NM23ACD210 Glutamate receptor 3 NMD A Receptor 2ACD212 Glutamate receptor 4 NMD A Receptor 2B CD213aI Glutaminase NMDE2CD213a2 Glutamine Synthetase NMDZ1CD217 Glutaredoxin 2 NMNA2CD218a Glutathione NEM nMycCD22 Glutathione NEW nNOSCD22 (pY822) Glutathione Peroxidase 1 NNTMCD22.2 Glutathione Peroxidase 4 NociceptinCD220 Glutathione Reductase Nod2Glutathione S TransferaseCD220 [alpha] [theta] 2 NodalCD221 Glutathione S Transferase I°1 NogginCD221 (pY1131) Glutathione S Transferase I‘ / i NONOCD222 Glutathione Synthetase Nonspecific Cytotoxic Cells CD223 Glycogen synthase 1 Notch 1CD224 Glycoprotein IX Notch2CD226 Glycoprotein VI Notch3CD227 GM-CSF Notch4CD229 GMI30 NOX2CD229.1 GM3.2 NOX4CD23 GNB2 NOXA2CD230 GNB2L1 NPCCD231 GNLY NPM-ALKCD233 GNMT NPM / B23 Phospho (Thr199)NPM / B23 PhosphoCD234 GnRHR(Thr234 / Thr237)CD235a Golgi Protein (58K) NPY5RCD235ab Golgi Zone NQOlCD236 GOLM1 NR2EICD239 GOLPH2 NR2C2CD24 GOSR1 Nrf2CD240CE gp340 NRG3CD240DCE gp49R NSPA / BCD243 GPA33 NT ALCD244 GPCR5C NTF97CD244.1 GPR-120 NucleolinCD244.2 GPR-143 Nucleolin Phospho (Thr76 / Thr84)Docket No. SLIN-032 / 01WO 217N-432617-WOCD245 GPR-151 NucleophosminCD246 GPR-18 NUDCCD247 GPR-30 NUMA1CD247 (pY142) GPR-40 Nuf77CD249 GPR-48 0 acetyl GD3CD25 GPR-49 Oct2CD252 GPR-50 Oct3 / 4CD253 GPR-56 Oct3 / 4ACD254 GPR-73A Oct4CD255 GPR-73B ODAGCD256 GPR-77 OGDHCD257 GPR-83 OLIG1CD258 GPR-86 OLIG2CD26 GPR-C5C Oligodendrocyte Marker CD261 GPR-C5D Oligodendrocyte Marker 01 CD262 Granulin Oligodendrocyte Marker 04 CD263 Granulysin Oncostatin M Receptor CD264 Granzynie A OrailCD265 Granzyme B OSCARCD266 Granzyme K 0SR1CD267 GRAP2 OsteonectinCD268 GRASP 1 OsteopontinCD269 GRASP65 OsteoprotegerinCD27 GRB2 Otx2CD270 GRB7 OVA (SIINFEKL) H-2Kb CD271 GRHPR Oval Cell MarkerCD272 GRIM 19 OvalbuminCD273 GRK1 Ovarian Carcinoma-associated AntigenCD274 GRK2 OX-62CD275 GRK3 pl 10 [delta]CD276 GRK5 pl 20 CateninCD277 GRK6 pl 20 Catenin (pS268)CD278 Growth hormone receptor p!20 Catenin (pS288)CD279 GRP 170 pl20 Catenin (pS879)CD28 GRP94 pl 20 Catenin (pT310) CD280 GSC p!20 Catenin (pT916) CD281 GSK3 [alpha] p!20 Catenin (pY228) CD282 GSK3 [alpha] / [beta] p!3CD283 GSK3 [beta] p!30CD284 GSPT2 pl 30 CasCD284 / MD2 Complex GST p!30 Cas (pY249)CD286 GST Epitope Tag pl4ARFCD289 GSTA4 p!50,95CD29 GTF2D1 p!9ARFDocket No. SLIN-032 / 01WO 217N-432617-WOCD290 GTPase HRAS p21CD294 GTPBP4 p22phoxCD298 Guanylate kinase p23CD299 H-2 p27KiplCD2a H-2. B131 P2RX4CD3 H-2Db P2RY8CD3 / CD44 H-2Dd P2X3CD30 H-2Kd P2X7CD300 H2-M P2Y6CD300a H2-M3 p34Cdc-2CD300e H2A. X p38CD300f H2A. X Phospho (Serl39) p38 MAPK (pT180 / pY182) CD301 H2A1J p400CD303 H60 p53CD303a HA tag p53 Acetylated (Lys305) CD304 HADHA p53 Acetylated (Lys382) CD305 HADHA / HADHB p53 Phospho (Serl5) CD307d HADHB p53 Phospho (Ser37)CD309 HADHSC p53 Phospho (Ser392)CD31 HAND1 p53BPl (Serl778)CD310 HAO1 p57Kip2CD312 Haptoglobin p60 CAF1CD314 HARS p62CD314 (activating) HARS2 p63CD314 (blocking) HBF p63 (IA)CD317 hCG [alpha] p70 S6 Kinase [beta]CD318 hCG[beta] p90 RskCD319 hCG[beta]4 p90 Rsk Phospho (Thr368 / Ser372) CD32 HCN4 p95 NBS1CD321 HDAC1 p97CD323 HDAC10 PA28 [gamma]CD324 HDAC2 PABP1CD325 HDAC3 PABP2CD326 HDAC4 PABPN1CD328 HDAC6 PAC1CD329 HDAC9 PAD2CD32B HDHD1A PAG1CD33 HDHD2 PAK1CD334 HDJ2 PAK2CD335 HDLBP PAK3CD336 HE4 pan ActinCD337 HEC1 pan MacrophageCD338 HEF1 Panendothelial Cell AntigenCD339 Helios PARIDocket No. SLIN-032 / 01WO 217N-432617-WOCD34 Hematopoiesis relatedParainfluenza Vims type 1 MacrophageCD340 Hematopoietic LineageParainfluenza Vims type 2 CocktailCD344 Hematopoietic Progenitor Cell Parainfluenza Virus type 3 CD349 Hemoglobin PARCCD35 Hemoglobin F PARD3CD351 Hemoglobin subunit [alpha] PARK7 / DJ1CD354 Hepatitis B Virus PARP. Cleaved Form Hepatitis B Vims CoreCD357 PARP16AntigenCD358 Hepatitis B Vims E Antigen PARP4CD36 Hepatitis B Vims SurfaceAntigen (Ad / Ay) PARVACD360 Hepatitis C Vims Pax2CD361 Hepatitis C Vims Core Pax5AntigenCD36L1 Hepatitis C Virus NS4 Pax6CD37 Hepsin Pax7CD38 HER2 Pax8CD39 HER3 Pax9CD39L4 HER4 PaxillinCD3D Hesl Paxillin Phospho (Tyril 8) CD3G Hexokinase Paxillin Phospho (Tyr31) CD3 [gamma] Hexokinasel PBEFCD3 [delta] Hexokinase2 PBKCD3 [epsilon] HFE1 PBPCD3 [epsilon] (CD 3HGF PBRMolecular Complex)CD4 HGFA Inhibitor 1 PBX3CD4 (domain 1) HHEX PCBCD4 (domain 2) HHV8 GPCR PCNACD4 v4 HIBCH PCYT1ACD40 HID1 PD-1HCD40bp HIF-1 [alpha] PD-ECGFCD41 HIF-2 [alpha] PDC-TREMCD41 / CD61 H1F1AN PDCD4CD41a HINT1 PDCD6CD41b HIP2 PDE3BCD42a HIPK2 PDECGFCD42b Hippocalcin PDGF-AACD42d Histamine H3 Receptor PDICD43 Histocytes PDK1CD44 Histone Hl PDK2CD44 (v3) Histone H1.0 PDPK 1CD44 (v4) Histone H2A PDPK1 (pS241)Docket No. SLIN-032 / 01WO 217N-432617-WOCD44 (v5) Histone H2B PDX1CD44 (v6) Histone H2B type IB PDZK1CD44 (v7) Histone H3 PECD44.2 Histone H3 Phospho (SerlO) PECRCD44std Histone H3 Phospho (Ser28) PEI-T ransferrinfecti on CD44v6 Histone H3.3 Pellino 1CD44var (v 10) Histone H4 Pentraxin 3CD44var (v3) HIV1 Core Antigen PEPDCD44var (v3-vl0) HIV1 pl7 PerforinCD44var (v4) HIV1 p24 Peroxiredoxin 1CD44var (v5) HIV1 p55 / pl7 Peroxiredoxin 2CD44var (v6) HIV1 tat Peroxiredoxin 6CD44var (v7) HIL60 PEX5CD44var (v7-v8) HLA Class I PF4CD45 HLA-2Kb / 2Db PGC1 [alpha]CD45.1 HLA-2kb / 2Dd PGISCD45.2 HLA-A PGP9.5CD45R HLA-A / B / C PGRP-IaCD45RA HLA-A1 / A11 / A26 PGRP-SCD45RB HLA-A1 / A36 PHD1CD45RC HLA-A10 / A11 PHD2CD45RO HLA-A10 / A28 / B75 Phosphatidy IserineCD46 HLA-A 10 / B62 / B71 Phospho SHIPPhospholipase A2 activator protein CD47 HLA-A11(PLAP)CD48 HLA-A2 Phospholipase C [beta] 3 CD49a HLA-A2 / A25 / A32 Phospholipase C [gamma] 1 CD49a / CD29 HLA-A2 / A28 Phospholipase DICD49b HLA-A2 / A3 / A29 Phosphoserine / threonine / tyrosine CD49b / CD29 HLA-A2 / A69 Phosphotyrosine CD49b / CD61 HLA-A2 / B17 PI 3 Kinase catalytic subunit [alpha]PI 3 Kinase catalytic subunit CD49c HLA-A2 / B5[gamma]CD49d HLA-A2 / B57 PI 3 Kinase pl 10 [beta] CD49d / CD29 HLA-A23 / A24 PI 3 Kinase pl 10 [delta] CD49e HLA-A24 / A11 / A2403 PI 3 Kinase pl 50 CD49e / CD29 HLA-A25 PI 3 Kinase p85 [alpha] CD49f HLA-A25 / A26 PI 4 kinase [beta] CD49f / CD29 HLA-A25 / A26 / A34 PIAS1CD4 [alpha] HLA-A25 / A32 PIAS3CD5 HLA-A26 / A34 / B71 / B62 PICK1CD5.1 HLA-A29 PIM1CD5.2 HLA-A3 PIM2CD5.6 HLA-A30 / A31 PintCD50 HLA-A33 / B8 PINK1Docket No. SLIN-032 / 01WO 217N-432617-WOCD51 HLA-A34 / B71 / A26 PIP5K2 [alpha]CD51 / 61 HLA-A9 PIP 5KI [gamma]CD52 HLA-A9 / A25 / A32 PIR-A / BCD53 HLA-A9 / A32 / B13 Pirh2CD54 HLA-B PISTCD55 HLA-B 12 PITX3CD56 HLA-B 13 / B62 / B 15 PIWIL2CD57 HLA-B 14 PKARII[alpha] (pS99) CD58 HLA-B 17 PKARII[beta] (pS114) CD59 HLA-B 17 / B35 / B44 PKA2[beta]CD59a HLA-B21 / B70 / B55 PKAR2CD6 HLA-B27 / B44 / B47 PK A [gamma]CD60b HLA-B35 / B57 / B75 / B77 PKCCD61 HLA-B44 / B75 / B 17 PKCqCD62E HLA-B48 / B60 PKC[alpha]CD62L HLA-B5 / B49 / B56 PKC[alpha] (pT497)CD62P HLA-B7 PKC[alpha] (pT638)CD63 HLA-B8 PKC[beta]CD64 HL A-B8 / B 14 PKC[beta]2CD64 a,b alloantigens HLA-BC PKC[gamma]CD64.1 HLA-Bw4 / A9 / A32 PKC[delta]CD65 HLA-Bw6 PKC [epsilon]CD65s (CD65 sialylated) HLA-Bw6 / B77 PKC[zeta]CD66 HLA-class I free chain PKC[theta]CD66a HLA-D PKC[eta]CD66a / b / c / e HLA-DM PKNCD66a / c / d HLA-DO PKN2CD66a / c / d / e HLA-DP PKRCD66a / c / e HLA-DQ PKX1CD66a / e HLA-DQ / DR PLA2G1BCD66b HLA-DQ 1 / DQ3 Placental alkaline phosphatase CD66c HLA-DQ 1 / DR7 Placental Protein 14CD66c / e HLA-DQ3 Plakophilin 3CD66e HLA-DQ6 Plastin LCD66f HLA-DQ7 PlateletCD68 HLA-DQA1 PLAUCD69 HLA-DQB1 PLC[gamma]1CD7 HLA-DQwl PLC[gamma]l (pY783) CD70 HLA-DR PLC[gamma]2CD70b HLA-DR / DP PLC[gamma]2 (pY759) CD71 HLA-DR / DP / DQ PlectinCD72 HLA-DR1 PleiotrophinCD72 a,b,c alloantigens HLA-DR11 PlexinAlCD72 b,c alloantigens HLA-DR3 / DR6 PlexinB2Docket No. SLIN-032 / 01WO 217N-432617-WOCD72.1 HLA-DR4 PLGFCD73 HLA-DR7 PLK1CD74 HLA-DR7 / DR[beta] PLK1 Phospho (Thr210) CD75 HLA-DR8 / DR12 PLK4CD77 HLA-DR9 PLSCR1CD78 HLA-DRA PLVAPCD79a HLA-DR[beta] PLZFCD79b HLA-DR[beta]3 PMCA(l-4)CD8 HLA-E PMCA4CD80 HLA-G PMEL17 / SILVCD81 HLCS PMNCD82 HLF PMP70CD83 HLXB9 PMS2CD84 HMG14 PNAdCD85 HMG17 PNPHCD85a HMG4 PodocalyxinCD85d HMGB1 PodoplaninCD85g HMGB2 POKEMONCD85h HMOX1 Polyhistidine TagCD85j HMOX2 PON1CD85k HNF4 [alpha] PON 3CD86 hnRNPA1 PP2A[alpha]CD87 hnRNPCl / C2 PP2 A [alpha] [beta]CD88 hnRNPD PPM1ACD89 hnRNPK PPP1ACD8 [alpha] hnRNPL PPP5CCD8 [alpha].1 hnRNPU PPP6CCD8[alpha].2 hnRNPULl PR3CD8[beta] Homing Receptor PR AlCD9 HOXB4 PRC1CD90.1 HOXB5 Pre-BCRCD90.2 HP 1 [alpha] Pre-T Cell Receptor [alpha] Chain CD90.9 HPal PrealbuminCD91 HPa2 PresenilinlCD91 [alpha] HPD Presenilin2CD91[beta] HPdl Prion protein PrPCD93 HPd2 PRKRACD94 HPil PRLRCD95 HPi2 PRMT1CD96 HPi3 PRMT5CD97 HPi4 pro Relaxin 1 / 2CD98 HPR1 pro Relaxin 2CD98hc HPRT1 Profilin1CD99 HPV16 E1 / E4 Progesterone ReceptorDocket No. SLIN-032 / 01WO 217N-432617-WOCD99R HPx1 ProhibitinCoagulation Factor VII DSCAM-L1 Eph Receptor A5CXCL 1 / 2 / 3 FLRT1 Ephrin B2DDR2 Frizzled-6 CD316DPCR1 Glypicanl KremenlDipeptidyl peptidase 6 IGSF4B Eph Receptor B 1Epithelial membraneIL-1R9 PlexinB3protein 3Endoglycan BAZ2B DMBT1Calgranulin C BRD4 FcRnFATP2 Kell L1MPI1FATP5 Kremen2 MUCDHLFcRLB LAX1 Patched 1GLP-2R CD85c SLC39A4GLUT3 MIF IGSF4AGlypican6 Neprilysin2 PRAT4BGPR-22 OBCAM HHV8-ORF74GPR-37 PlexinCl 4E-BP1 Phospho (Thr36 / 45) GPR-37L1 RGM-B 4E-BP1 Phospho (Thr69) INSRR Wilms' Tumor protein 1 DCAR1LINGO 1 Xg Von Hippel-LindauLINGO2 DCBLD2 Isotype ControlmGluR2 ASAM Granzyme MmGluR7 Desmocollinl REA Isotype Control MMP25 Frizzled-3 CD300LGNeuromedin B Receptor MMP24 MR1NRAGE TOR CD327Osteoactivin WNT3a B7-H6Porimin Glypican5 CLEC4GProkineticin Receptor 1 Jaggedl / Jagged2 BATF3Prominin2 Pax3 IL-38Semaphorin 3 A CF. LSR2 Monocarboxylic Acid Transporter 1 SLAP-130 CyclinDl / D2 MC5RSomatostatin Receptor 5 PlexinA2 TCF7SCARF 1 TAFA5 TM4SF1STAMP2 FR4 GPR-49 (CRL Region) TAFA3 CD315 CD 156aTAFA4 NKG2I ADAMS 3TM4SF18 RAMP2 ADAMTS13Tuberous Sclerosis 1 TNFRH3 CCL16TCF8 Biotin CXCL 17CMG2 GPVI DeltexlIL-17D Receptor MS4A4B FBXO15Macrophage StimulatingPIR-B GPR34Protein ReceptorDocket No. SLIN-032 / 01WO 217N-432617-WOSiglec-11 Semaphorin 4F GPRC5ASyndecan3 1L-1F6 ProinsulinTGF-[beta]R3 CD39L3 JAK1CD85e Contactin 3 MEP1ASOX7 CLEC4B Hypocretin receptor 2Activin A Receptor Typep70S6KIA MC3RCarbohydrate PGRP-L RAE- 1 [epsilon] Sulfotransferase 15CD300b PLET1 STRA6CELSR3 ADAM9 Fc[gamma]RIIACoagulation Factor II AMIGO3 Insulin R / IGF-I R Heterotetramer DC-SCRIPT CD99-L2 SPARCL1CD79 [alpha] cy CD92 XBP1Prokineticin 1 SULT1A1 XBP1 (COOH terminus) Prokineticin 2 SULT1A3 / SULT1A4 XBP5Prolactin SULT1C2 XCL1ProMBPl SULT2A1 XIAPProstaglandin D2 Receptor SUMO1 XPCProstaglandinSUMO2 XPNPEP3dehydrogenase 1Prostaglandin E Receptor XRCC2EP3 SUMO3Prostate Cell SurfaceAntigen SUN1 XTP4t genProstate Specific Antigen Suppressor of Fused YAP1Prostatic Acid Phosphatase SUPT16H YB1Proteasome 20 S C2 Survivin YES1Proteasome 20 S [alpha] 2 Survivin Phospho (Thr34) YY1S V40 Large T and Small tProteasome 20S [alpha]3 ZAP-70AntigensProteasome 20S [alpha] 5 SWC1a ZAP-70 (pY292)Proteasome 20S [alpha]6 SWC6 ZAP-70 (pY319)Proteasome 20S [alpha]7 SYBL1 ZAP-70 (pY319) / Syk (pY352) Proteasome Syk ZBP-120S[alpha]1 / 2 / 3 / 5 / 6 / 7Protein A Syk (pY348) ZIPKProtein G Synapsin I ZO-1 (Mid)Protein Kinase D2 Synapsin II ZONAB (Mid)Protein Phosphatase Synaptojanin2 Zyxin1 [beta]Protein phosphotaseinhibitor 1 Synaptophysin IL-33RProtein S Syndecan4 Globo HProteinase ActivatedSynGAP CCL8Receptor 4Prothrombin Synip Siglec-GPSA-NCAM Syntaxin CD307eDocket No. SLIN-032 / 01WO 217N-432617-WOPSD95 Syntaxin6 CLEC6Pseudomonas Aeruginosa Syntrophin SnaillSMAD1 (pS463 / pS465) / SMAD8 PSMA SYWC (pS465 / pS467)SMAD2 (pS465 / pS467) / SMAD3 PSMD14 T cells (pan reactive)(pS423 / pS425)Psoriasin T Lymphocytes GSK-3[beta] (pY216)PT APR T- and B-Cell Activation NKX6.1AntigenPTBP1 T7 tag FAK (pY397)PTEN TAB1 Btk (pY223) / Itk (pYl 80) PTGER2 TACE ERK3PTGER4 TACI CD276[beta]PTHLH TAF172 MCP-3PTK7 TAF250 FcApRPTP1B TAG72 CD238PTP4A2 Talinl beta2 Microglobulin [b,c] PTPS Talin2 NucleosteminPTPI' / i Tamm Horsfall (Uroniucoid) GPR-49 (Central LRR) PTRH2 TANK! GPR-49 (N-Terminal)PU.l TAPI Phospholipase C [beta]4 PU60 TAP2 coilinPUMA TARDBP HNFl[beta]PUMA [gamma] TARP TrinitrophenalTartrate-resistant acidPumiliol Annexin VIIphosphatasePumilio2 TAS1R1 CD301aPXR Tau CD301bPYCARD TBA1B mTOR (pS2448)Pygopus2 Tbet PI16Pyk2 TBK1 (pS172) MSC (W5C5)Pyk2 (pY402) TBX1 LAMP5Pyruvate DehydrogenaseTC10 GPR-19El [alpha]Pyruvate Dehydrogenase TCF3 FPRL2E2Pyruvate Dehydrogenase TCF7L1 CXCL5E2 / E3bpq2 TCF7L2 PAR2Qal(b) TCL1 PDGF-R[alpha]Qa2 TCP 1 [alpha] ULBP6RABI 1A TCP 1 [beta] ULBP2 / 5 / 6RAB25 TCR IL-17B ReceptorRAB27A TCRDOI1.10 ULBP3RAB4 TCR HY Arginase IRAB5a TCR V[alpha] 11 Alkaline PhosphataseRAB9 TCRV[alpha]ll.l / H.2Kd ULBP3Docket No. SLIN-032 / 01WO 217N-432617-WORael TCR V[alpha]2 TrkBRacl / Cdc42 TCR V[alpha]24 OsteocalcinRAD 17 TCR V[alpha]24-J [alpha] 18 IL-22R[alpha]lRAD17 Phospho (Ser645) TCR V[alpha]3.2 APIRAD23A IFN-[alpha] / [beta] Receptor Subunit TCR V[alpha]3.2b,c 2RAD51 TCR V[alpha]7.2 FGFR3RAD54 TCR V[alpha]8 SR- AlRAD9A TCR V[alpha]8.3 Rae-1 (pan)Radixin TCR V[beta] 1 CXCL12RAE- 1 [gamma] TCR V[beta] 10a TRENDRAE- 1 [delta] TCR V[beta]10b BrachyuiyRAFI TCRV[beta]ll CLEC5ARAGE TCR V[beta]12 Integrin [alpha]7RAIDD TCR V[beta]12b MerRainbow Trout Ig TCRV[beta]13 XCR1RalBPl TCR V[beta]13.1 AML2RanBP9 TCR V[beta] 13.2 von Willebrands factor A2 RanGAPl TCR V[beta] 13.6 NIMP7RAP1A / RAP1B TCR V[beta]14 GLP-1RRAP 1 GAP TCRV[beta]16 FR1Raptor TCRV[beta]17 IL-lRAcPRARfalpba] TCR V[beta] 17[alpba] Claudin-6RAS TCRV[beta]18 Leptin ReceptorRASGAP TCR V[beta]2 Caherin 6RASGRF1 TCR V[beta]20 IL-1R type IIRASSF1 A TCR V[beta]21.3 Nectin4Rb TCR V[beta]22 Delta like protein 3Rb (a.a. 332-344) TCR V[beta]23 ChemR23Rb (pS780) TCR V[beta]3 GPR-39Rb (pS807 / pS811) TCR V[beta]4 CD158b2RbAp46 TCR V[beta]5 IL- 10R [alpha]RbAp48 TCR V[beta]5.1 LRIG1RBC TCR V[beta]5.1 / 5.2 Neuropilin2RBC (Polyclonal Rabbit) TCR V[beta]5.2 IL-10R[beta]RBM35A TCR V[beta]5.3 IL-18R[beta]RBP4 TCR V[beta]6 GPR-44RBX1 TCR V[beta]7 Eph Receptor B2RCC1 TCR V[beta]7.1 Glypican3RcRL6 TCR V[beta]7.2 IFN-[gamma]R2Red Blood Cell TCR V[beta]8 IL-17C ReceptorRelaxin 1 TCR V[beta]8.1 / 8.2 BMPR1BRelaxin 1 / 2 TCR V[beta]8.2 IL-3 IRARelaxin 2 TCR V[beta]8.2 / 8.3 OCILRelB TCR V[beta]8.2 / 8.4 Frizzled-7Docket No. SLIN-032 / 01WO 217N-432617-WORELMfbeta] TCR V[beta]8.3 IL-26RELT TCR V[beta]8.5 GPR-15Renin TCR V[beta]9 PlexinDlRENT1 TCR V[gamma] 1.1 CD158Reptin TCR FPR1V[gamma] 1. l / [gamma] 1.2Repulsive GuidanceTCR V[gamma]2 HBEGFMolecule CResistin TCR V[gamma]3 Vitamin D3REST TCR V[gamma]9 PlexinB 1Ret TCR Vfdeltajl Somatostatin Receptor 2 Reticular Fibroblasts and TCR V[delta]2 OV-6Reticular FibresReticulonlA TCR V[delta]4 CXCL16Reticulum Cells TCR V[delta]6.3 / 2 Siglec-ERetinoblastoma 1 TCR [alpha] EDG5RFLAT1 TCR [alpha] [beta] Ninjurin-1RFP TCR [beta] Integrin [alpha] 9RGS6 TCR [gamma] [delta] MHC Class II (I-Ed / j / k / p / r / u / v) RGS7 TCR [zeta] ThBRGS9 TCT'P MAP-2 (2a & 2b)RUEB TdT IgM IN-chainRho Tec MHC Class I (H-2b / p)RhoA TEF1 MHC Class I (H-2s / p / q / d / u / r) RHOC TEM8 MHC Class I (H-2s / f) RhoGAP Tenascin C CDw60RhoGDI TERI 19 Bad Phospho (Seri 12)RIAM TERF2 Caspase 3 Cleaved (Asp 175)Tenninal-DeoxynucleotidylR1CTOR Clik 1 Phospho (Ser345)TransferaseRIG1 TERT Chk2 Phospho (Thr68)RIP1 Tetranectin Cyclin D 1 Phospho (Thr286) RIP2 TFF3 cFos Phospho (Ser32) Rituximab TFIIB FosBRLADQ TGF-[beta] GSK-3[beta] (pSer9) RLADR TGF-[beta]l Histone H3 Acetylated (Lys9) RNA polymerase II TGF-[beta]3 HSI Phospho (Tyr397)RNA polymerase II CTDTGF-[beta]Rl Hsp27 Phospho (Ser82) repeat YSPTSPSRNASE-L TGF-[beta]R2 ID3RNASE 1 TGN38 CD221[beta]RNF144B TGN46 Phospho-IRAK4 (Thr345 / Ser346) RNF168 TRAP 11 Phospho-cJun (Ser73) RNF36 THEMIS S6 (pS240 / pS244)RNPEP Thioredoxin Syk (pY525 / pY526)ROCK1 Thioredoxin Reductase 1 C23Docket No. SLIN-032 / 01WO 217N-432617-WOROR1 TliPOK Hemoglobin [beta]ROR2 Thrombin Receptor CD221 [alpha]ROR[alpha] Thrombocyte p27RORfgamma] Thrombospondin c Jun Phospho (Ser63 )ROS Thymidine Kinase 1 PP AR [gamma] RPA32ZRPA2 Thyroglobulin ENPPlRPA70 TIA-1 PILR [alpha]RPS6 TIAM2 PILR[beta]RSF1 Tiel TwistlRSK 1 p90 Tie2 (p¥1102) Cadherin MRSK2 Tie2 (pY992) CD302RSK3 TIFT [beta] Phospho (Ser473) CD66dRSK4 TIGIT CLEC14ART1A Timl CD242RTlAa Tim2 Syndecan2RTlAa, b Tim3 IL-32 [alpha]RTlAa, b,l Tim3 Fc Fusion Protein CDORTlAc Tim4 CrypticRTlAu Tim50 EndothelinB ReceptorRT1B Timeless FR3RT6.1 TIMP1 IGSF3RT6.2 TIMP2 CD85IRyanodine Receptor TIP49A MatriptaseRYK TIRAP MCEMP1RyR TISllb mGluR4S-Tag TL1A StabilinlSI 00 Al TLK1 Stabilin2S100A10 TLR11 Cadherin 13S100A13 TLR12 GPR-109AS100A4 CD285 TSPAN8S100A6 TLR7 ReglAS100A9 TLR8 Cadherin 12SI 00 [alpha] TMEFF2 ECE1S100[alpha]2 TMPS2 FABP5S100[beta] TMSA IGSF4CS6 (pS235 / pS236) TMTSP Trem-like 1S6 (pS240) TNAP Activin A Receptor Type IIA S6 (pS244) TNAP3 ALK7S6K TNF- [alpha] BCAMSAA4 TNF-[beta] BLAMESall4 TNFR Related Protein CEACAM4Salmonella Paratyphi A TNPO3 Claudin-3Salmonella Typhimurium Tollip CLP24Salmonid Ig (H and L TOMM20 CRHR1chain)Docket No. SLIN-032 / 01WO 217N-432617-WOSalmonid Ig (H chain) TOMM22 DC-STAMPSAM68 TOPI Eph Receptor B 3SAMD2 TOP2A FATP4SAP TOP2B FcRLlSARA TORC2 FcRL2SATB1 Torsin A FcRL3SATB2 TOX FSH-RSC5A5 TPH1 Gi24SC6A4 TPPP Histamine Hl ReceptorSCAT TPTE Neu5GcSCD1 TRUE Lin28AScramblasel TRA-1-60 IL-33R[alpha]SCYl-like 3 TRA-1-60R ATM (pSerl981)SDF1 TRA-1-81 Integrin [alpha] 8SDF1 [alpha] TRA-2-49 Integrin [beta] 7SDHA TRA-2-54 Integrin [beta] 8SDHB TRADD CD158kSecretory component TRAF2 KORSecurin TRAF4 CD851SELP TRAF5 LRIG3Sema4A TRAF6 LRP4Sema7A TRAM2 MMP16SENP1 Transferrin MS4A4ASEPPI T ransglutaminase NAALADase-like 2SERCA2 Transglutaniinase2 Neuropeptide Y receptor type 1 SerpinB 1 Transketolase Oncostatin M Receptor [beta] SerpinB2 TRAP1 MS4A3SerpinB6 TRAPPC2 PEAR1Sestrinl TRAP[alpha] PEDF ReceptorSFRP2 Trem-like 2 PlexinA4SGK1 Trem-like 4 ProtocadherinlSHC1 TRIB2 ROBO2Shigella Bovdii TRIB3 ROBO4SHIP1 TRIM EDG8SHP1 TRIM25 Scavenger receptor A5SHP2 TRIM29 Semaphorin 4ASHP2 (pY542) TRK Semaphorin 4BSIAH2 TrkA Semaphorin 6ASIGIRR TrkC Siglec-16Siglec-10 Trop2 Somatostatin Receptor 3 Siglec-8 Tropomyosin 1 STINGSiglec-9 TROY GPBAR1Siglec-F TRPC6 TM4SF4Siglec-H TRPM2 TMEM87ADocket No. SLIN-032 / 01WO 217N-432617-WOSIK2 TRPM8 TSPAN2SIRT1 TRX1 VEGF-R1,2,3Trypanosoma brucei MajorSIRT2 ADAM 15Lysosomal ProteinSIRT3 Trypanosoma brucei procyclin Calreticulin2(EP)SIRT5 Trypanosoma congolenseprocyclin Complement Factor H-related 4 SIT1 Try panosoma cruzi LPG CXCL6SIX2 TSC2 Phospho (Ser664) CD158a / h / b2 / f / gSKP1A TSC2 Phospho (Thrl462) Ea52-68 peptide bound to I-Ab SLA-DR TSG101 HLA-Bw4Sian TSHR ATF1 Phospho (Ser63) SLC1A3 TSLP EpiregulinSLC1A7 TSLP Receptor FATP1SLC22A1 TSPO FibromodulinSLC22A5 TTF1 FurinSLC26A6 Tubb3 GalaninSLC26A7 Tuberin IL-11SLC30A4 Tubulin [alpha] CD306SLC39A11 Tubulin [alpha] IB MFG-E8SLC4A3 Tubulin [alpha]4a MINASLC6A19 Tubulin [alpha] 3E Oct4ASLC6A6 Tubulin [alpha] 8 OLIG1,2,3SLC7A10 Tubulin [beta] Oncostatin MSLC7A14 Tubulin [beta] class III Semaphorin 3ESLC7A3 Tubulin [beta]4 SlugSLC7A8 Tubulin [gamma] SOX3tumor antigens of epithelialSLC8A2 origin STYK1SLC9A6 Twist2 LTBP1SLP76 TXNIP TIMP3SLP76 (pY128) TYK2 VAP-BSM22 [alpha] TYMS WNT9aSMAC Tyro3 5HT2CSMAC3 Tyrosinase AATKSMAD1 Tyrosine Hydroxylase ACLPSMAD1 (pS463 / 465) UACA ADAMTS15SMAD1 / 5 UBA52 alpha IB Adrenoreceptor SMAD1 / 9 UBC9 APLPISMAD2 UBE2 Fluorescein / Oregon Green SMAD2 / 3 (pS465 / 467)UBE2L3DELETE RXR-[beta]SMAD3 UBE2L6 L3MBTL3SMAD4 UBE2M CCL1SMAD5 UBE2N PRDM4Docket No. SLIN-032 / 01WO 217N-432617-WOSMAD6 UBF ACTHSMC1 UBF1 PDZ binding kinaseSMC IL 1 Ubiquitin HuC / HuD neuronal protein SMN UBK63 TDRD3Smoothelin UCH37 EP300SMURF2 UCK Carbonic Anhydrase VI SNAP25 UCP2 Cholecystokinin A Receptor SNX1 UCP3 CCL23SO ATI UFM1 CDleSOCS1 ULBP1 ChondrolectinSOCS2 ULBP2 Chordin-Like 2SOCS3 ULBP4 Claudin-lObSOCS6 ULK3 Claudin-11SOD2 UNC5A Claudin-12Sodium Potassium ATPase UNC5B CIaudin-17Sonic Hedgehog UNG CLEC2ASortilin uPA Spi-BSOSC3 UQCRC1 TRAMSOX1 UQCRC2 Carboxypeptidase ESOXIO Urml Islet Cell Autoantigen 1 SOX17 URP2 Patched2SOX18 USF1 ST8SIA2SOX2 USP11 AML1 (pS249)SOX2 (COOH terminus) USP13 AMPK[beta]l (pS182)SOX2 (NH2 terminus) USP22 BRF1 / 2SOX9 USP28 Histone H3 Phospho (Tlirl 1) SP-D USP7 MEK1 (pT286)Spl UTF1 MMP16Sp3 V5 tag MNK Phospho (T197 / T202) Spectrin [alpha] 1 VAMP5 / 8 NUMBSPHK1 VAP1 Hsp27 Phospho (Ser78)Sptl6 VASA PKC[theta] (pT538)Src (pY418) VASP SIRT1 (pS47)SREBP1 VAV1 ZAP-70 (pY493)ssDNA VAV2 ZAP-70 (pY315 / pY319) SSEA3 VAV3 sRAGESSEA4 VDAC1 mCherryPI 3 Kinase regulatory subunit SSEA5 VEGF[alpha]SSH3BP1 VEGF-120 TIMP4SSR2 VEGF-A SRCSSR5 VEGF-R1 ZAP-70 (pT493)SSRP1 VELIS-3 TSC2 Phospho (S939) SSX2IP VGLU1 RagCStat 1 Villin SHIP2Docket No. SLIN-032 / 01WO 217N-432617-WOStall (N-Terminus) Vimentin MKK4 (pS257)Stat 1 (pS727) Vinculin CD79a (pY182)Stall (pY701) Viperin TRAF1Stall [alpha] VIPR1 EV IIStat2 Vitamin D Binding protein SRC3Stat3 Vitamin D Receptor SOX 11Stat3 (pS727) Vitronectin IL-17F homodimerStat3 (pY705) VMAT2 CCRL1Stat4 vMyb / cMyb FOXP2Stat4 (pY693) von Willebrands factor IFNAR2Stat5 VRK1 REA ControlStat5 (pY694) VSV-G tag CD228Stat5a WAPL Muc-13Stat5b WASP P2X7RStat6 WC14 Btk (pY223 / ltk (pY180)State (pY641 ) WC15 CD248Stathmin / Opl8 PhosphowCD44 GILT(Serl6)Stathmin 1 WIP (pS488) RecoverinStefin B WNT1 Cardiac Troponin IStem Cell Factor WNT16 PTF1 [alpha]STIM1 WNT2 NKX2.2STK3 WNT5B HLA-B7 / B27STK33 WNT6 Myosin light chain 2aSTK39 WSTF Myosin light chain 2vSTOM WWOX Epithelial AntigenSTRO1 Xanthine OxidaseEXAMPLESEXAMPLES|0151] The present invention is further illustrated by reference to the following Examples. However, it should be noted that these Examples, like the embodiments described above, are illustrative and are not to be construed as restricting the scope of the invention in any way.Example 1: Screening of immune co-stimulatory and adhesion molecules

[0152] To screen for immune co-stimulatory and adhesion molecules that may enhance the potency of the hydrogel particles for inducing proliferation, expansion, and / or activation of immune cells, Human Atlas database was analyzed for molecules expressed on BCMA and CD19 cell lines, and the result were subjected to various fdters (e.g., filters for (i) I' cell and cell surface protein; and (ii) specific pathways). Multiple immune co-stimulatory or adhesionDocket No. SLIN-032 / 01WO 217N-432617-WOmolecules (also referred to herein as “enhancers”), including ICAM-l, CD80, CD86, CD40L, and CD70 were identified in the screening. A subset of these immune co-stimulatory and adhesion molecules were tested for enhancement of antigen-mediated activation.Example 2: Addition of at least one of the adhesion molecules or co-stimulatory molecules enhances BCMA CAR-T activation

[0153] Synthetic hydrogel beads with an average size of 20 um and comprising a polyacrylamide matrix were synthesized to produce cell mimics. The cell mimics were further bioconjugated with an adhesion or a co-stimulatory molecule (also referred to herein as “enhancer”) selected from CD40L, CD70, CD80, CD86, or ICAM-l alone to produce “Mimics + Enhancer” or in combination with BCMA to produce “Mimics + BCMA + Enhancer”. Cell mimics without any conjugation to enhancer or BCMA and mimics only conjugated to BCMA were also used as controls. The conjugated cell mimics were screened for enhancement of BCMA-specific CAR-T activation. Activation was measured using a cytokine release assay measuring interferon gamma (IFNv) secreted in the supernatant. 100k BCMA CAR-T cells (BPS Biosciences, Cat # 78660) were co-incubated with 500k cell mimics (i.e., a 1:5 E: T effector to target ratios) in a 96-well non-treated plate in 10% FBS+RPMI media. Supernatants from BCMA CAR-T were collected after 24 hours and stored at -20 degree Celsius. Upon completion of experiment, collected supernatants were analyzed by the BD Cytometric IFNv Bead assay (BD Biosciences, Cat # 560379) to quantify IFNy release.

[0154] The results in FIG. 1 demonstrate that ICAM-l conjugation or CD86 conjugation to hydrogel beads comprising an immune cell antigen BCMA enhances the ability of such hydrogel beads to activate IFNy secretion by the corresponding immune cells by about 2-fold, CD70 conjugation or CD80 conjugation to hydrogel beads comprising an immune cell antigen also enhances the ability of such hydrogel beads to activation IFNy secretion by the corresponding immune cells.Example 3: Addition of at least one of the adhesion molecules or co-stimulatory molecules enhances (2D 19 CAR-T activation

[0155] Synthetic hydrogel beads with an average size of 20 um and comprising a polyacrylamide matrix were synthesized to produce cell mimics. The cell mimics were conjugated with CD19 to produce “Mimics with CD19”. The cell mimics were further bioconjugated with an adhesion or a co-stimulatory molecule (also referred to herein asDocket No. SLIN-032 / 01WO 217N-432617-WO“enhancer") selected from CD86 and ICAM-1 in combination with CD 19 to produce “Mimics with CD 19 and CD86” and “Mimics with CD 19 and ICAM-1”. lire conjugated cell mimics were screened for enhancement of CD19-specific CAR-T activation. Activation was measured using a cytokine release assay measuring Interferon gamma (IFNy) secreted in the supernatant.100k CD19 CAR-T cells (BPS Biosciences. Cat#78171) were co-incubated with 100k cell mimics (a 1:1 E: T effector to target ratio) in a 96-well non-treated plate in 10% FBS+RPMI media. Supernatants were collected after 18 hours and stored at -20 degree Celsius, Upon completion of experiment, collected supernatants were analyzed by the BD Cytometric IFNy Bead assay (BD Biosciences, Cat # 560379) to quantify IFNyrelease.|0156] As shown in FIG 2, synthetic hydrogel beads bioconjugated with CD 19 and ICAM-1 or CD 19 and CD 86 molecules displayed higher activation induction of CD 19 CAR-T cells than hydrogel beads bioconjugated with CD 19 only.Example 4: Addition of the adhesion molecule ICAM-1 to hydrogel particles enhances BCMA CAR-T activation in potency assays at multiple time points and ratios

[0157] Hydrogel beads bioconjugated with BCMA and ICAM-1 molecules displayed increased activation levels of BCMA CAR-T cells upon incubation at 6-hour, 24- hour, and 48-hour time points. Activation was measured using a cytokine release assay measuring Interferon gamma (IFNy) secreted in the supernatant. 100k BCMA CAR-T cells (BPS Biosciences, Cat # 78660) were co-incubated with 500k cell mimics (i.e., a 1:5 E: T effector to target ratios) in a 96-well non-treated plate in 10% FBS+RPMI media. Supernatants ere collected at multiple time points (6, 24, and 48hrs) and stored at -20 degree Celsius. Upon completion of experiment, collected supernatants were analyzed by the BD Cytometric IFNy Bead assay (BD Biosciences, Cat # 560379) to quantify IFNy release. A biological cell line MM, IS (BCMA expressing cell line) was used as the positive assay control and cell mimics without any bioconjugation w'ere used as the negative control. BCMA beads from ACROBiosystems were also used as a control.

[0158] The results in FIG. 3 demonstrate that ICAM-1 conjugation to hydrogel beads comprising an immune cell antigen enhances the ability of such hydrogel beads to activate IFNg secretion by the corresponding immune cells by about 2-fold across all time points, s shown in FIG. 3, hydrogel beads bioconjugated with both BCMA and ICAM-1 matched biological cells in terms of the ability to activate IFNg secretion at the 48-hour time point, whereas hydrogel beads bioconjugated with BCMA but not ICAM-1 resulted in lower IFNyDocket No. SLIN-032 / 01WO 217N-432617-WOsecretion levels that were similar to those of BCMA beads from ACROBiosystems across all time points.

[0159] The levels of secreted Interleukin-2 (IL-2) in the supernatant at 6-hour, 24-hour, and 48-hour time points were also analyzed using a cytokine release assay. 100k BCMA CAR-T cells (BPS Biosciences, Cat#78660) were co-incubated with hydrogel beads bioconjugated with different biomolecules (a 1:5 E: T effector to target ratios) in a 96-well non-treated plate in 10% FBS+RPMI media. Supernatants were collected at multiple time points (6, 24, and 48hrs) and stored at -20 degree Celsius. Upon completion of experiment, collected supernatants were analyzed by the BD Cytometric IL-2 Bead assay (BD Biosciences, Cat # 558270) to quantify IL-2 release. A biological cell line MM. IS (BCMA expressing cell line) was used as the positive assay control and cell mimics without any bioconjugation were used as the negative control. BCMA beads from ACROBiosystems were also used as a control. As shown in FIG.4, activation with hydrogel beads bioconjugated with BCMA resulted in significantly higher levels of IL-2 secretion, compared to activation with BCMA beads from ACROBiosys tems, at 24-hour and 48-hour time points, and inclusion of ICAM-1 in the hydrogel beads resulted in further increase of IL-2 secretion levels across all time points.

[0160] The levels of secreted Interferon-gamma (IFNy) in the supernatant at an 18-hour time point were also analyzed at 1:1 E: T ratio, 100k BCMA CAR-T cells (BPS Biosciences, Cat#78660) were co-incubated with 100k cell mimics (a 1:1 E T effector to target ratios) in a 96-well U -bottom plate in 10% FBS+RPMI media. Supernatants were collected at 18 hours and stored at -20 degree Cel sius. Upon completion of experiment, collected supernatants were analyzed by the BD Cytometric IFNg Bead assay (BD Biosciences, Cat # 560379) to quantify IFNy release. A biological cell line H929 (BCMA expressing cell line) was used as the positive assay control. Cell mimics without any bioconjugation and beads bioconjugated to ICAM-1 alone were used as the negative control. As shown in FIG. 5, activation with hydrogel beads bioconjugated with BCMA at 1: 1 E: T ratio resulted in IFNy secretion, and inclusion of ICAM-1 with BCMA in the hydrogel beads resulted in further increase of IFNy secretion levels without increase in background IFNy secretion in the absence of BCMA on hydrogels.Example 5: Addition of the adhesion molecule ICAM-1 to hydrogel particles enhances CD 19 CAR-T activation in potency assays without background activation

[0161] Hydrogel beads bioconjugated with CD 19 and ICAM-I molecules displayed increased activation levels of CD19 CAR-T cells upon incubation at 6-hour and 18-hour time points.Docket No. SLIN-032 / 01WO 217N-432617-WOActivation was measured using a cytokine release assay measuring Interferon gamma (IFNy) secreted in the supernatant. 100k CD19 CAR-T cells (BPS Biosciences, Cat # 78171) or 100k donor-matched untransduced control T cells (BPS Biosciences, Cat # 78170) were coincubated with 500k cell mimics (i.e., a 1:5 E: T effector to target ratios) in a 96-well non¬ treated plate in 10% FBS+RPM1 media. Supernatants were collected at multiple time points (6 and 18 hours) and stored at -20 degree Celsius. Upon completion of experiment, collected supernatants were analyzed by the BD Cytometric IFNg Bead assay (BD Biosciences, Cat # 560379) to quantify IFNy release. CD19 beads from ACROBiosystems and two biological cell lines Raji and Daudi (CD19 expressing cell lines) were used as the positive assay control. Unconjugated hydrogel beads and hydrogel beads bioconjugated to ICAM-1 only were used as the negative control.

[0162] Tire results in FIG.6 demonstrate that ICAM-1 conjugation to hydrogel beads does not induce CD 19 CAR-T activation without CD 19 co-conjugation comprising an immune cell antigen. However, the addition of ICAM-1 to CD 19 enhances the ability of such hydrogel beads to activate IFNg secretion by the CD 19 CAR-T cells, but not donor-matched activated untransduced T cells. Cytokine release from CAR-T co-cultured with immune cell antigen and enhancer was on par with cell lines and superior to CD 19 microbeads, at 6 hours of co-culture. Similar trends in specific activation were observed at 18 hours of co-culture, as shown in FIG 7. Furthermore, the results in FIG 7 show background activation -was observed from co-culture of untransduced T cells and cell lines at 18 hours, but not from co-culture of untransduced unconjugated mimics or mimics bioconjugated to ICAM- 1 only and not comprising an immune cell antigen.Example 4: Addition of the adhesion molecule ICAM-1 to hydrogel particles enhances CD20 CAR-T activation in potency assays

[0163] Hydrogel beads bioconjugated with CD20 and ICAM-1 or ICAM-1 only were co¬ cultured with CD20-specific CAR-T for 24 hours. 100k CD20 CAR-T (BPS Cat #78611) were co-cultured with 100k hydrogel beads of indicated conjugation or CD20-expressing cell line Raji in FIG 8. Co-culture was performed in 96-well plate in 10%FBS + RPMI media and activation was measured by level of Interferon gamma (IFNg) in supernatant. CD20 CAR-T secreted IFNy upon co-culture with hydrogel mimics bioconjugated to ICAM-1 and CD20 comprising an immune cell antigen, but not ICAM-1 alone. As a positive control, CD20+ Raji cells were used to provide specific activation.Docket No. SLIN-032 / 01WO 217N-432617-WO

[0164] All, documents, patents, patent applications, publications, product descriptions, and protocols which are cited throughout this application are incorporated herein by reference in their entireties for all purposes.

[0165] Tire embodiments illustrated and discussed in this specification are intended only to teach those skilled in the art the best way known to the inventors to make and use the invention. Modifications and variation of the above-described embodiments of the invention are possible without departing from the invention, as appreciated by those skilled in the art in light of the above teachings. It is therefore understood that, within the scope of the claims and their equivalents, the invention may be practiced otherwise than as specifically described.Docket No. SLIN-032 / 01WO 217N-432617-WONUMBERED EMBODIMENTS OF THE DISCLOSURE

[0166] Notwithstanding the appended claims, the disclosure sets forth the following numbered embodiments:1. A synthetic particle, comprising:a polymer matrix;at least one antigen comprising an extracellular domain (ECD) of a protein recognized by an engineered immune receptor, wherein the ECD is configured to induce an antigendependent functional response from a plurality of immune effector cells expressing the engineered immune receptor; andat least one immune co-stimulatory or adhesion biomolecule.2. The synthetic particle of embodiment 1, wherein the ECD is configured in a substantially native-like configuration to induce the antigen-dependent functional response.3. The synthetic particle of embodiment 1, wherein the at least one antigen comprises a full-length protein comprising the ECD, and wherein the full-length protein is configured in a substantially native-like configuration to induce the antigen-dependent functional response.4. The synthetic particle of any one of embodiments 1-3, wherein the plurality of immune effector cells expressing the engineered immune receptor comprise CAR-T cells, CAR-NK cells, CAR-macrophage cells, or combinations thereof.5. The synthetic particle of any one of embodiments 1-4, wherein the at least one antigen comprises CD19, CD20, or B-cell maturation antigen (BCMA).6. The synthetic particle of any one of embodiments 1-5, wherein the at least one immune co-stimulatory or adhesion biomolecule is selected from the group consisting of: Intercellular Adhesion Molecule 1 (ICAM-1) or a functional fragment thereof, a biomolecule that activates the signaling of CD28, a biomolecule that activates the signaling of CD27, a biomolecule that activates the signaling of CD40, and any combinations thereof,7. Hie synthetic particle of embodiment 6, wherein:DocketNo. SLIN-032 / 01WO 217N-432617-WO(a) the biomolecule that activates the signaling of CD28 comprises (i) CD80 or a functional fragment thereof and / or (ii) CD86 or a functional fragment thereof;(b); the biomolecule that activates the signaling of CD27 comprises CD70 or a functional fragment thereof; or(c) the biomolecule that activates the signaling of CD40 comprises CD40L or a functional fragment thereof.8. The synthetic particle of embodiment 7, wherein the immune co-stimulatory or adhesion biomolecule comprises ICAM-1 or the functional fragment thereof, CD80 or a functional fragment thereof, CD86 or a functional fragment thereof, CD70 or a functional fragment thereof, CD40L or a functional fragment thereof, or any combination thereof.9. The synthetic particle of any one of embodiments 1-8, wherein the polymer matrix is derived from one or more monomers selected from the group consisting of: hydroxyethyl methacrylate, ethyl methacrylate, 2-hydroxyethyl methacrylate (HEMA), propylene glycol methacrylate, N -vinylpyrrolidone (N VP), methyl methacrylate, glycidyl methacrylate, glycerol methacrylate (GMA), glycol methacrylate, lactic acid, glycolic acid, poly(lactic-co-glycolic) acid (PLGA), ethylene glycol, fumaric acid, 2-hydroxyethyl methacrylate, hydroxyethoxyethyl methacrylate, hydroxydiethoxyethyl methacrylate. methoxyethyl methacrylate, meth oxy ethoxy ethyl methacrylate, methoxy diethoxy ethyl methacrylate, poly (ethylene glycol) methacrylate, methoxy-poly(ethylene glycol) methacrylate, methacrylic acid, sodium methacrylate, glycerol methacrylate, hydroxypropyl methacrylate, hydroxybutyl methacrylate, phenyl acrylate, phenyl methacrylate, benzyl acrylate, benzyl methacrylate, 2-phenylethyl acrylate, 2-phenylethyl methacrylate, 2 -phenoxy ethyl aer late, 2 -phenoxyethyl methacrylate, phenylthioethyl acrylate, phenylthioethyl methacrylate, 2,4,6-tribromophenyl acrylate, 2,4,6- tribromophenyl methacrylate, pentabromophenyl acrylate, pentabromophenyl methacrylate, pentachlorophenyl acrylate, pentachlorophenyl methacrylate, 2,3-dibromopropyl acrylate, 2,3-dibromopropyl methacrylate, 2-naphthyl acrylate, 2 -naphthyl methacrylate, 4-methoxybenzyl acrylate, 4-methoxybenzyl methacrylate, 2-benzyloxyethyl acrylate, 2-benzy loxyethy I methacrylate, 4-chlorophenoxyethyl acrylate, 4-chlorophenoxyethyl methacrylate, 2- phenoxyethoxyethyl acrylate, 2-phenoxyethoxyethyl methacrylate, N-phenyl acrylamide, biphenyl methacrylamide, N-benzyl acrylamide, N-benzyl methacrylamide, N, N-dibenzyl acrylamide, N, N-dibenzyl methacrylamide, N -diphenylmethyl acrylamide N-(4- methylphenyl)methyl acrylamide, N-l -naphthyl acrylamide, N-4-nitrophenyl acrylamide, N-Docket No. SLIN-032 / 01WO 217N-432617-WO(2-phenylethyl)acrylamide, N-triphenylmethyl acrylamide, N-(4-hydroxyphenyl)acrylamide, N, N-methylphenyl acrylamide, N. N-phenyl phenylethyl acrylamide, N -diphenylmethyl methacrylamide, N-(4-methyl phenyl )methyl methacrylamide, N-l -naphthyl methacrylamide, N-4-nitrophenyl methacrylamide, N-(2-phenylethyl)methacrylamide, N-triphenylmethyl methacrylamide, N-(4-hydroxyphenyl)methacrylamide, N, N -methylphenyl methacrylamide, N, N'-phenyl phenylethyl methacrylamide, acrylamide, bisacry lamide, streptavidin-acrylamide, N-vinylcarbazole, 4-vinylpyridine, 2-vinylpyridine, agar, agarose, alginic acid, alguronic acid, alpha glucan, amylopectin, amylose, arabinoxylan, beta-glucan, callose, capsulan, carrageenan polysaccharide, cellodextrin, cellulin, cellulose, chitin, chitosan, chrysolaminarin, curdlan, cyclodextrin, alpha-cyclodextrin, dextrin, dextran, ficoll, fructan, fucoidan, galactoglucomannan, galactomannan, galactosamine galactan, gellan gum, glucan, glucomannan, glucorunoxylan, glycocalyx, glycogen, hemicellulose, homopolysaccharide, hypromellose, icodextrin, inulin, kefiran, laminarin, lentinan, levan polysaccharide, lichenin, mannan, mixed-linkage glucan, paramylon, pectic acid, pectin, pentastarch, phytoglycogen, pleuran, polydextrose, polysaccharide peptide, porphyran, pullulan, schizophyllan, sinistrin, sizofiran, welan gum, xanthan gum, xylan, xyloglucan, zymosan, and any combinations thereof.10. The synthetic particle of any one of embodiments 1-9, wherein the polymer matrix is derived from one or more monomers comprising acrylamide.11. The synthetic particle of any one of embodiments 1-10, wherein the polymer matrix is a hydrogel matrix.12. Tire synthetic particle of embodiment any one of embodiments 1-11, wherein the synthetic particle is configured to determine functional potency of the plurality of immune effector cells expressing the engineered immune receptor.13. A population of synthetic particles, comprising:at least one antigen comprising an extracellular domain (ECD) of a protein recognized by an engineered immune receptor, wherein the ECD is configured to induce an antigendependent functional response from a plurality of immune effector cells expressing tire engineered immune receptor;at least one immune co-stimulatory or adhesion biomolecule; and whereinDocket No. SLIN-032 / 01WO 217N-432617-WOeach synthetic particle of the population of synthetic particles comprises a polymer matrix.14. Tlie population of synthetic particles of embodiment 13, wherein the at least one antigen and the at least one immune co-stimulatory or adhesion biomolecule are conjugated to different synthetic particles.15. The population of synthetic particles of embodiment 13, wherein the at least one antigen and the at least one immune co-stimulatory or adhesion biomolecule are conjugated to the same synthetic particle.16. The population of synthetic particles of any one of embodiments 13-15, wherein the extracellular domain (ECD) is configured in a substantially native-like configuration to induce the antigen -dependent functional response from the plurality of immune effector cells expressing the engineered immune receptor.17. The population of synthetic particles of any one of embodiments 13-15, wherein the at least one antigen comprises a full-length protein comprising the ECD, and wherein the full-length protein is configured in a substantially native-like configuration to induce the antigen-dependent functional response.18. The population of synthetic particles of any one of embodiments 13-17, wherein the plurality of immune effector cells expressing the engineered immune receptor comprise CAR-T cells, CAR-NK cells, CAR-macrophage cells, or combinations thereof,19. Tlie population of synthetic particles of any one of embodiments 12-18, wherein the at least one antigen comprises CD19, CD20, or B-cell maturation antigen (BCMA)20. The population of synthetic particles of any one of embodiments 13-19, wherein the at least one immune co-stimulatory or adhesion biomolecule is selected from the group consisting of: Intercellular Adhesion Molecule 1 (ICAM-1) or a functional fragment thereof, a biomolecule that activates tire signaling of CD28, a biomolecule that activates the signaling of CD27, a biomolecule that activates the signaling of CD40, and any combinations thereof.Docket No. SLIN-032 / 01WO 217N-432617-WO21. The population of synthetic particles of embodiment 20, wherein:(a) the biomolecule that activates the signaling of CD28 comprises (i) CD80 or a functional fragment thereof and / or (ii) CD86 or a functional fragment thereof;(b) the biomolecule that activates the signaling of CD27 comprises CD70 or a functional fragment thereof; or(c) the biomolecule that activates the signaling of CD40 comprises CD40L or a functional fragment thereof.22. The population of synthetic particles of any one of embodiments 13-21, wherein the polymer matrix is derived from one or more monomers selected from group consisting of: hydroxyethyl methacrylate, ethyl methacrylate, 2-hydroxyethyl methacrylate (HEMA), propylene glycol methacrylate, N -vinylpyrrolidone (NVP), methyl methacrylate, glycidyl methacrylate, glycerol methacrylate (GMA), glycol methacrylate, lactic acid, glycolic acid, poly(lactic-co-glycolic) acid (PLGA), ethylene glycol, fumaric acid, 2-hydroxyethyl methacrylate, hydroxyethoxyethyl methacrylate, hydroxydiethoxyethyl methacrylate, methoxyethyl methacrylate, methoxyethoxyethyl methacrylate, methoxydiethoxyethyl methacrylate, polyethylene glycol) methacrylate, methoxy-poly(ethylene glycol) methacrylate, methacrylic acid, sodium methacrylate, glycerol methacrylate, hydroxypropyl methacrylate, hydroxybutyl methacrylate, phenyl acrylate, phenyl methacrylate, benzyl acrylate, benzyl methacrylate, 2-phenylethyl acrylate, 2-phenylethyl methacrylate, 2-phenoxyethyl acrylate, 2-phenoxyethyl methacrylate, phenylthioethyl acrylate, phenylthioethyl methacrylate, 2,4,6-tribrornophenyl acrylate, 2,4,6-tribromophenyl methacrylate, pentabromophenyl acrylate, pentabromophenyl methacrylate, pentachlorophenyl acrylate, pentachlorophenyl methacrylate, 2,3-dibromopropyl acrylate, 2,3-dibromopropyl methacrylate, 2 -naphthyl acrylate, 2 -naphthyl methacrylate, 4-methoxybenzyl acrylate, 4-methoxybenzyl methacrylate, 2-benzy loxyethy I acrylate, 2-benzyloxyethyl methacrylate, 4-chlorophenoxyethyl acrylate, 4-chlorophenoxyethyl methacrylate, 2-phenoxy ethoxy ethyl acrylate, 2 -phenoxy ethoxyethyl methacrylate, N-phenyl acrylamide, bi¬ phenyl methacrylamide, N-benzyl acrylamide, N-benzyl methacrylamide, N, N-dibenzyl acrylamide, N, N-dibenzyl methacrylamide, N-diphenylmethyl acrylamide N-(4-methylphenyl)methyl acrylamide, N-l -naphthyl acrylamide, N-4-nitrophenyl acrylamide, N-(2-phenyIethyI)acrylamide, N-triphenylmethyl acrylamide, N-(4-hydroxyphenyl)acrylamide, N, N-methylphenyl acrylamide, N, N-phenyl phenylethyl acrylamide, N-diphenylmethyl methacrylamide, N-(4-methyl phenyl)methyl methacrylamide, N-l -naphthyl methacrylamide,Docket No. SLIN-032 / 01WO 217N-432617-WON-4-nitrophenyl methacrylamide, N-(2-phenylethyl)methacrylamide, N-triphenylmethyl methacrylamide, N-(4-hydroxyphenyl)methacrylamide, N, N-methylphenyl methacrylamide, N, N'-phenyl phenylethyl methacrylamide, acrylamide, bisacrylamide, streptavidin-acrylamide, N-vinylcarbazole, 4-vinylpyridine, 2-vinylpyridine, agar, agarose, alginic acid, alguronic acid, alpha glucan, amylopectin, amylose, arabinoxylan, beta-glucan, callose, capsulan, carrageenan polysaccharide, cellodextrin, cellulin, cellulose, chitin, chitosan, chrysolaminarin, curdlan, cyclodextrin, alpha-cyclodextrin, dextrin, dextran, ficoll, fructan, fucoidan, galactoglucomannan, galactomannan, galactosamine galactan, gellan gum, glucan, glucomannan, glucorunoxylan, glycocalyx, glycogen, hemicellulose, homopolysaccharide, hypromellose, icodextrin, inulin, kefiran, laminarin, lentinan, levan polysaccharide, lichenin, mannan, mixed-linkage glucan, paramylon, pectic acid, pectin, pentastarch, phytoglycogen, pleuran, polydextrose, polysaccharide peptide, porphyran, pullulan, schizophyllan, sinistrin, sizofiran, welan gum, xanthan gum, xylan, xyloglucan, and zymosan,23. The population of synthetic particles of any one of embodiments 13-22, wherein the polymer matrix is a hydrogel matrix.24. The population of synthetic particles of any one of embodiments 13-23, wherein the population of synthetic particles is configured to determine functional potency of a plurality of immune effector cells expressing the engineered immune receptor.25. A method of evaluating potency of immune effector cells, comprising contacting the immune effector cells with the population of synthetic particles of any one of embodiments 13-24.26. The method of embodiment 25, wherein the method comprises evaluating the antigen dependent functional response from the plurality of immune effector cells.27. Tlie method of embodiment 26, wherein the antigen dependent functional response is determined by interferon-gamma (IFNy) secretion by the plurality of immune effector cells.28. The method of embodiment 26, wherein the antigen dependent functional response is determined by Interleukin-2 (IL -2) secretion by the plurality of immune effector cells.

Claims

Docket No. SLIN-032 / 01WO 217N-432617-WOCLAIMS1. A synthetic particle, comprising:a polymer matrix;at least one antigen comprising an extracellular domain (ECD) of a protein recognized by an engineered immune receptor, wherein the ECD is configured to induce an antigen¬ dependent functional response from a plurality of immune effector cells expressing the engineered immune receptor; andat least one immune co-stimulatory or adhesion biomolecule.

2. The synthetic particle of claim 1, wherein the ECD is configured in a substantially native-like configuration to induce the antigen -dependent functional response.

3. The synthetic particle of claim 1, wherein tire at least one antigen comprises a full-length protein comprising the ECD, and wherein the full-length protein is configured in a substantially native-like configuration to induce the antigen -dependent functional response.

4. The synthetic particle of any one of claims 1-3, wherein the plurality of immune effector cells expressing the engineered immune receptor comprise CAR-T cells, CAR-NK cells, CAR-macrophage cells, or combinations thereof.

5. Tire synthetic particle of any one of claims 1-4, wherein the at least one antigen comprises CD 19, CD20, or B-cell maturation antigen (BCMA).

6. lire synthetic particle of any one of claims 1-5, wherein the at least one immune co¬ stimulatory or adhesion biomolecule is selected from the group consisting of: Intercellular Adhesion Molecule 1 (ICAM-1) or a functional fragment thereof, a biomolecule that activates the signaling of CD28, a biomolecule that activates the signaling of CD27, a biomolecule that activates the signaling of CD40, and any combinations thereof.

7. The synthetic particle of claim 6, wherein:DocketNo. SLIN-032 / 01WO 217N-4.32617-WO(a) the biomolecule that activates the signaling of CD28 comprises (i) CD80 or a functional fragment thereof and / or (ii) CD86 or a functional fragment thereof;(b); the biomolecule that activates the signaling of CD27 comprises CD70 or a functional fragment thereof; or(c) the biomolecule that activates the signaling of CD40 comprises CD40L or a functional fragment thereof.

8. The synthetic particle of claim 7, wherein the immune co-stimulatory or adhesion biomolecule comprises ICAM-1 or the functional fragment thereof, CD80 or a functional fragment thereof, CD86 or a functional fragment thereof, CD70 or a functional fragment thereof, CD40L or a functional fragment thereof, or any combination thereof.

9. The synthetic particle of any one of claims 1-8, wherein the polymer matrix is derived from one or more monomers selected from the group consisting of: hydroxyethyl methacrylate, ethyl methacrylate, 2-hydroxyethyl methacrylate (HEMA), propylene glycol methacrylate. N- vinylpyrrolidone (NVP), methyl methacrylate, glycidyl methacrylate, glycerol methacrylate (GMA), glycol methacrylate, lactic acid, glycolic acid, poly(lactic-co-glycolic) acid (PLGA), ethylene glycol, fumaric acid, 2-hydroxyethyl methacrylate, hydroxyethoxyethyl methacrylate, hydroxydiethoxyethyl methacrylate, methoxyethyl methacrylate, methoxyethoxyethyl methacrylate, methoxydiethoxyethyl methacrylate, polyethylene glycol) methacrylate, methoxy-poly(ethylene glycol) methacrylate, methacrylic acid, sodium methacrylate, glycerol methacrylate, hydroxypropyl methacrylate, hydroxybutyl methacrylate, phenyl acrylate, phenyl methacrylate, benzyl acrylate, benzyl methacrylate, 2 -phenylethyl acrylate, 2- phenylethyl methacrylate, 2-phenoxyethyl acrylate, 2-phenoxyethyl methacrylate, phenylthioethyl acrylate, phenylthioethyl methacrylate, 2,4,6-tribromophenyl acrylate, 2,4,6- tribromophenyl methacrylate, pentabromophenyl acrylate, pentabromophenyl methacrylate, pentachlorophenyl acrylate, pentachlorophenyl methacrylate, 2,3 -dibromopropyl acrylate, 2,3-dibromopropyl methacrylate, 2 -naphthyl acrylate, 2 -naphthyl methacrylate, 4-methoxybenzyl acrylate, 4-methoxybenzyl methacrylate, 2-benzyloxyethyl acrylate, 2-benzyloxyethyl methacrylate, 4-chlorophenoxyethyl acrylate, 4-chlorophenoxyethyl methacrylate, 2-phenoxyethoxyethyl acrylate, 2-phenoxyethoxyethyl methacrylate, N-phenyl acrylamide, biphenyl methacrylamide, N-benzyl acrylamide, N-benzyl methacrylamide, N, N-dibenzyl acrylamide, N, N-dibenzyl methacrylamide, N -diphenylmethyl acrylamide N-(4-methylphenyl)methyl acrylamide, N-l -naphthyl acrylamide, N-4-nitrophenyl acrylamide, N-Docket No. SLIN-032 / 01WO 217N-432617-WO(2-phenylethyl)acrylamide, N-triphenylmethyl acrylamide, N-(4-hydroxyphenyl)acrylamide, N, N-methylphenyl acrylamide, N. N-phenyl phenylethyl acrylamide, N -diphenylmethyl methacrylamide, N-(4-methyl phenyl )methyl methacrylamide, N-l -naphthyl methacrylamide, N-4-nitrophenyl methacrylamide, N-(2-phenylethyl)methacrylamide, N-triphenylmethyl methacrylamide, N-(4-hydroxyphenyl)methacrylamide, N, N -methylphenyl methacrylamide, N, N'-phenyl phenylethyl methacrylamide, acrylamide, bisacry lamide, streptavidin-acrylamide, N-vinylcarbazole, 4-vinylpyridine, 2-vinylpyridine, agar, agarose, alginic acid, alguronic acid, alpha glucan, amylopectin, amylose, arabinoxylan, beta-glucan, callose, capsulan, carrageenan polysaccharide, cellodextrin, cellulin, cellulose, chitin, chitosan, chrysolaminarin, curdlan, cyclodextrin, alpha-cyclodextrin, dextrin, dextran, ficoll, fructan, fucoidan, galactoglucomannan, galactomannan, galactosamine galactan, gellan gum, glucan, glucomannan, glucorunoxylan, glycocalyx, glycogen, hemicellulose, homopolysaccharide, hypromellose, icodextrin, inulin, kefiran, laminarin, lentinan, levan polysaccharide, lichenin, mannan, mixed-linkage glucan, paramylon, pectic acid, pectin, pentastarch, phytoglycogen, pleuran, polydextrose, polysaccharide peptide, porphyran, pullulan, schizophyllan, sinistrin, sizofiran, welan gum, xanthan gum, xylan, xyloglucan, zymosan, and any combinations thereof.

10. The synthetic particle of any one of claims 1-9, wherein the polymer matrix is derived from one or more monomers comprising acrylamide.

11. The synthetic particle of any one of claims 1-10, wherein the polymer matrix is a hydrogel matrix.

12. The synthetic particle of any one of claims 1-11, wherein the synthetic particle is configured to determine functional potency of the plurality of immune effector cells expressing the engineered immune receptor.

13. A population of synthetic particles, comprising:at least one antigen comprising an extracellular domain (ECD) of a protein recognized by an engineered immune receptor, wherein the ECD is configured to induce an antigendependent functional response from a plurality of immune effector cells expressing the engineered immune receptor;at least one immune co-stimulatory or adhesion biomolecule; and whereinDocket No. SLIN-032 / 01WO 217N-432617-WOeach synthetic particle of the population of synthetic particles comprises a polymer matrix.

14. The population of synthetic particles of claim 13, wherein the at least one antigen and the at least one immune co-stimulatory or adhesion biomolecule are conjugated to different synthetic particles,15. The population of synthetic particles of claim 13, wherein the at least one antigen and the at least one immune co-stimulatory or adhesion biomolecule are conjugated to the same synthetic particle.

16. The population of synthetic particles of any one of claims 13-15, wherein the extracellular domain (ECD) is configured in a substantially native-like configuration to induce the antigen-dependent functional response from the plurality of immune effector cells expressing the engineered immune receptor.

17. The population of synthetic particles of any one of claims 13-15, wherein the at least one antigen comprises a full-length protein comprising the ECD, and wherein the full- length protein is configured in a substantially native-like configuration to induce the antigendependent functional response.

18. The population of synthetic particles of any one of claims 13-17, wherein the plurality of immune effector cells expressing the engineered immune receptor comprise CAR- T cells, CAR-NK cells, CAR-macrophage cells, or combinations thereof,19. The population of synthetic particles of any one of claims 13-18, wherein the at least one antigen comprises CD19, CD20, or B-cell maturation antigen (BCMA).

20. The population of synthetic particles of any one of claims 13-19, wherein the at least one immune co-stimulatory or adhesion biomolecule is selected from the group consisting of: Intercellular Adhesion Molecule 1 (ICAM-1) or a functional fragment thereof, a biomolecule that activates the signaling of CD28, a biomolecule that activates the signaling of CD27, a biomolecule that activates the signaling of CD40, and any combinations thereof.Docket No. SLIN-032 / 01WO 217N-432617-WO21. The population of synthetic particles of claim 20, wherein:(a) the biomolecule that activates the signaling of CD28 comprises (i) CD80 or a functional fragment thereof and / or (ii) CD86 or a functional fragment thereof;(b) the biomolecule that activates the signaling of CD27 comprises CD70 or a functional fragment thereof; or(c) the biomolecule that activates the signaling of CD40 comprises CD40L or a functional fragment thereof.

22. The population of synthetic particles of any one of claims 13-21, wherein the polymer matrix is derived from one or more monomers selected from group consisting of: hydroxyethyl methacrylate, ethyl methacrylate, 2-hydroxyethyl methacrylate (HEMA), propylene glycol methacrylate, N -vinylpyrrolidone (NVP), methyl methacrylate, glycidyl methacrylate, glycerol methacrylate (GMA), glycol methacrylate, lactic acid, glycolic acid, poly(lactic-co-glycolic) acid (PLGA), ethylene glycol, fumaric acid, 2-hydroxyethyl methacrylate, hydroxyethoxyethyl methacrylate, hydroxydiethoxyethyl methacrylate, methoxyethyl methacrylate, methoxyethoxyethyl methacrylate, methoxydiethoxyethyl methacrylate, polyethylene glycol) methacrylate, methoxy-poly(ethylene glycol) methacrylate, methacrylic acid, sodium methacrylate, glycerol methacrylate, hydroxypropyl methacrylate, hydroxybutyl methacrylate, phenyl acrylate, phenyl methacrylate, benzyl acrylate, benzyl methacrylate, 2-phenylethyl acrylate, 2-phenylethyl methacrylate, 2-phenoxyethyl acrylate, 2-phenoxyethyl methacrylate, phenylthioethyl acrylate, phenylthioethyl methacrylate, 2,4,6-tribrornophenyl acrylate, 2,4,6-tribromophenyl methacrylate, pentabromophenyl acrylate, pentabromophenyl methacrylate, pentachlorophenyl acrylate, pentachlorophenyl methacrylate, 2,3-dibromopropyl acrylate, 2,3-dibromopropyl methacrylate, 2 -naphthyl acrylate, 2 -naphthyl methacrylate, 4-methoxybenzyl acrylate, 4-methoxybenzyl methacrylate, 2-benzyloxyethyl acrylate, 2-benzyloxyethyl methacrylate, 4-chlorophenoxyethyl acrylate, 4-chlorophenoxyethyl methacrylate, 2-phenoxy ethoxy ethyl acrylate, 2 -phenoxy ethoxyethyl methacrylate, N-phenyl acrylamide, bi¬ phenyl methacrylamide, N-benzyl acrylamide, N-benzyl methacrylamide, N, N-dibenzyl acrylamide, N, N-dibenzyl methacrylamide, N-diphenylmethyl acrylamide N-(4-methylphenyl)methyl acrylamide, N-l -naphthyl acrylamide, N-4-nitrophenyl acrylamide, N-(2-phenyIethyI)acrylamide, N-triphenylmethyl acrylamide, N-(4-hydroxyphenyl)acrylamide, N, N-methylphenyl acrylamide, N, N-phenyl phenylethyl acrylamide, N-diphenylmethyl methacrylamide, N-(4-methyl phenyl)methyl methacrylamide, N-l -naphthyl methacrylamide,Docket No. SLIN-032 / 01WO 217N-432617-WON-4-nitrophenyl methacrylamide, N-(2-phenylethyl)methacrylamide, N-triphenylmethyl methacrylamide, N-(4-hydroxyphenyl)methacrylamide, N, N-methylphenyl methacrylamide, N, N'-phenyl phenylethyl methacrylamide, acrylamide, bisacrylamide, streptavidin-acrylamide, N-vinylcarbazole, 4-vinylpyridine, 2-vinylpyridine, agar, agarose, alginic acid, alguronic acid, alpha glucan, amylopectin, amylose, arabinoxylan, beta-glucan, callose, capsulan, carrageenan polysaccharide, cellodextrin, cellulin, cellulose, chitin, chitosan, chrysolaminarin, curdlan, cyclodextrin, alpha-cyclodextrin, dextrin, dextran, ficoll, fructan, fucoidan, galactoglucomannan, galactomannan, galactosamine galactan, gellan gum, glucan, glucomannan, glucorunoxylan, glycocalyx, glycogen, hemicellulose, homopolysaccharide, hypromellose, icodextrin, inulin, kefiran, laminarin, lentinan, levan polysaccharide, lichenin, mannan, mixed-linkage glucan, paramylon, pectic acid, pectin, pentastarch, phytoglycogen, pleuran, polydextrose, polysaccharide peptide, porphyran, pullulan, schizophyllan, sinistrin, sizofiran, welan gum, xanthan gum, xylan, xyloglucan, and zymosan,23. The population of synthetic particles of any one of claims 13-22, wherein the polymer matrix is a hydrogel matrix.

24. The population of synthetic particles of any one of claims 13-23, wherein the population of synthetic particles is configured to determine functional potency of a plurality of immune effector cells expressing the engineered immune receptor.

25. A method of evaluating potency of immune effector cells, comprising contacting the immune effector cells with the population of synthetic particles of any one of claims 13- 24.

26. The method of claim 25, wherein the method comprises evaluating the antigen dependent functional response from the plurality of immune effector cells.

27. The method of claim 26, wherein the antigen dependent functional response is determined by interferon-gamma (IFNy) secretion by the plurality of immune effector cells.

28. The method of claim 26, wherein the antigen dependent functional response is determined by Interleukin-2 (IL-2) secretion by the plurality of immune effector cells.

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