Methods and compositions for T cell activation

1. A synthetic dendritic cell (synthetic DC) comprising:

a delivery agent, wherein the delivery agent is a hydrogel substrate comprising an oxidized alginate-gelatin covalently cross-linked (ADA-GEL) hydrogel;

a linker;

a binding moiety; and

at least one T cell activation agent;

wherein the linker is coupled to the delivery agent, the binding moiety is coupled to the linker, and the T cell activation agent is coupled to the binding moiety; and

wherein the synthetic DC is capable of initiating activation and expansion of T cells.

2. The synthetic DC of claim 1 ,

wherein the delivery agent has a stiffness between about 1 kPa and about 30 kPa.

3. The synthetic DC of claim 1 ,

wherein the linker comprises a bi-functional hydrophilic polyethylene glycol (PEG)-based linker; and

wherein the linker provides a flexible, extended reach to provide improved access to a T cell.

4. The synthetic DC of claim 1 , wherein the binding moiety comprises avidin, streptavidin, or neutravidin.

5. The synthetic DC of claim 1 , wherein the T cell activation agent comprises

one or more compositions selected from the group consisting of a MHC, a non-classical MHC, CD1a, CD1c, CD1d, pMHC, anti-CD28 (αCD28), CD70, CD40, CD5, CD80, CD86, and a cytokine and corresponding cytokine receptor selected from Interleukin 15 (IL15)/IL-15Rα, IL-2, IL-7, IL-12, or 4-1BBL; and

OX40L.

6. The synthetic DC of claim 1 , wherein the T cell activation agent comprises

one or more compositions selected from the group consisting of MHC, pMHC, anti-CD28 (αCD28), Interleukin 15 (IL 15 )/IL-15Rα, IL-2, IL-7, IL-12, CD1a, CD1c, CD1d, CD70, CD40, CD5, CD80, or CD86; and

wherein the T cell activation agent is conjugated to a peptide or peptide tetramer, or wherein the T cell activation agent is multimeric.

7. The synthetic DC of claim 1 , comprising one or more agents capable of neutralizing negative co-stimulatory regulators on T cells selected from the group consisting of anti-CTLA-4, anti-PDL-1, anti-PD-1, anti-IL13R, or anti-IL4R.

8. The synthetic DC of claim 1 , in fluid contact with T cells provided by a subject in need of a therapeutic treatment.

9. The synthetic DC of claim 8 , wherein the synthetic DCs enable a high-throughput production of subject-specific T cells.

10. A method of generating a synthetic dendritic cell (DC) comprising:

(i) providing a hydrogel delivery agent comprising an oxidized alginate-gelatin covalently cross-linked (ADA-GEL) hydrogel;

(ii) providing a linker;

(iii) providing a binding moiety;

(iv) providing one or more T cell activation agents;

(v) coupling the linker to the hydrogel delivery agent;

(vi) coupling the linker to the binding moiety; and

(vii) coupling the binding moiety to the one or more T cell activation agents.

11. A method of activating T cells comprising:

(i) providing a synthetic DC according to claim 1 ; and

(ii) providing a T cell in fluid contact with the synthetic DC.

12. A method for expanding T cells against individualized tumor-specific mutational antigens or shared antigen comprising:

(i) providing T cells, optionally from a tumor biopsy or blood;

(ii) providing a synthetic DC of claim 1 ;

(iii) activating the T cells comprising contacting the T cell and the synthetic DC;

(iv) incubating the T cells and the synthetic DC for a period of time sufficient to induce T cell activation; and

(v) administering the activated T cells to a subject.

13. A method of treating cancer or chronic disease in a subject in need thereof comprising:

(i) providing T cells, optionally from a tumor biopsy or blood;

(ii) providing a synthetic DC of claim 1 ;

(iii) activating the T cells comprising contacting the T cell and the synthetic DC;

(iv) incubating the T cells and the synthetic DCs for a period of time sufficient to induce T cell activation; and

(ii) administering the activated T cells to the subject.