Injectable Cryogel Vaccine Devices and Methods of Use Thereof

Abstract

The invention provides polymer compositions for cell and drug delivery.

1 . An injectable cancer vaccine device comprising a cell-adhesive cryogel composition comprising open interconnected macropores,
 wherein said cryogel composition comprises at least 75% pores,   wherein said cryogel composition is characterized by shape memory following deformation by compression through a needle,   wherein said cryogel composition comprises a crosslinked gelatin polymer or a crosslinked alginate polymer, and   wherein said cryogel composition comprises a cancer antigen.   
     
     
         2 . The device of  claim 1 , wherein said gelatin or alginate is acrylated or methacrylated. 
     
     
         3 . The device of  claim 1 , wherein the device recruits a cell into the cryogel composition upon injection into a subject. 
     
     
         4 . The device of  claim 3 , wherein the cryogel composition is degraded by the recruited cell. 
     
     
         5 . The device of  claim 1 , wherein the cryogel composition is formed by cryopolymerization of methacrylated gelatin or methacrylated alginate. 
     
     
         6 . The device of  claim 5 , wherein the cryogel comprises a methacrylated gelatin macromonomer concentration of 0.5% to 1.4% (w/v). 
     
     
         7 . The device of  claim 1 , wherein said cryogel composition comprises a living attenuated cancer cell. 
     
     
         8 . The device of  claim 1 , wherein said composition comprises a biomolecule in one or more of said open interconnected pores. 
     
     
         9 . The device of  claim 8 , wherein said biomolecule comprises a small molecule, nucleic acid, or protein. 
     
     
         10 . The device of  claim 9 , wherein said protein comprises GM-CSF. 
     
     
         11 . The device of  claim 9 , wherein said nucleic acid comprises a CpG nucleic acid oligonucleotide (CpG-ODN). 
     
     
         12 . The device of  claim 1 , wherein the cryogel composition is between 100 μm 3  to 100 mm 3  in size. 
     
     
         13 . A method for eliciting an anti-cancer immune response, comprising administering to a subject the device of  claim 1 . 
     
     
         14 . The method of  claim 13 , wherein the device is injected into the subject once to 5 times in the lifetime of the subject. 
     
     
         15 . The method of  claim 13 , wherein the injected device comprises at least 0.5×10 6  immune cells at least 1 day after injection into the subject. 
     
     
         16 . The method of  claim 13 , wherein the injected device comprises 10 7  or fewer cells 15 days or more after injection. 
     
     
         17 . The method of  claim 13 , wherein the injected device, a tissue within 10 cm of the injected device, or both comprises an elevated level of a cytokine compared to the level of the cytokine at a site in the subject more than 10 cm away from the injected device. 
     
     
         18 . The method of  claim 13 , wherein the device increases the survival time of at least 80% of subjects diagnosed with a cancer by at least 1 month compared to the survival time of an untreated subject, wherein increased survival time is determined by comparing the prognosis for survival in the subject from a time period prior to administration of the device to the prognosis for survival in the subject following administration of the device, wherein an increase in predicted survival time indicates that the treatment increased survival of the subject following administration of the device. 
     
     
         19 . The method of  claim 13 , wherein the device reduces the rate of tumor growth in the subject compared to the rate of tumor growth in an untreated subject. 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the cancer comprises melanoma. 
     
     
         22 . The method of  claim 1 , wherein the living attenuated cancer cell comprises an attenuated melanoma cell. 
     
     
         23 . The method of  claim 22 , wherein the attenuated melanoma cell is an irradiated melanoma cell. 
     
     
         24 . The method of  claim 8 , wherein the biomolecule comprises a pathogen-associated molecular pattern (PAMP). 
     
     
         25 . The method of  claim 8 , wherein the biomolecule comprises a cytokine. 
     
     
         26 . The method of  claim 25 , wherein the cytokine comprises Chemokine (C—C motif) ligand 5 (CCL5), eotaxin, interleukin-1alpha (IL-1α), IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, GM-CSF, macrophage inflammatory protein-1alpha (MIP-1α), MIP-1β, keratinocyte-derived chemokine (KC), tumor necrosis factor-alpha (TNF-α), granulocyte-colony stimulating factor (G-CSF), interferon-alpha (IFN-α), IFN-γ, or monocyte chemotactic protein-1 (MCP-1). 
     
     
         27 . The device of  claim 1 , wherein said cryogel composition comprises macropores having a diameter of 20 μm to 300 μm. 
     
     
         28 . The device of  claim 1 , wherein said cryogel composition is characterized by shape memory following deformation by compression through a needle, such that said cryogel returns to its original undeformed three-dimensional shape less than one second after compression through the needle. 
     
     
         29 . The device of  claim 1 , wherein said highly crosslinked cryogel composition comprises a crosslinking density of at least 50% polymer crosslinking. 
     
     
         30 . The device of  claim 1 , wherein said highly crosslinked cryogel composition comprises a crosslinking density of 50-100% polymer crosslinking. 
     
     
         31 . The device of  claim 1 , further comprising microspheres. 
     
     
         32 . The device of  claim 31 , wherein said microspheres comprise PLGA. 
     
     
         33 . The device of  claim 31 , wherein said microspheres are physically entrapped within the cryogel composition. 
     
     
         34 . The device of  claim 31 , wherein said microspheres comprise GM-CSF. 
     
     
         35 . The device of  claim 31 , wherein said microspheres comprise a drug. 
     
     
         36 . A syringe comprising (i) a needle; (ii) a reservoir comprising the device of  claim 1 ; and (iii) a plunger. 
     
     
         37 . The syringe of  claim 36 , comprising a 16-gauge, an 18-gauge, a 22-gauge, a 24-gauge, a 26-gauge, a 28-gauge, a 30-gauge, a 32-gauge, or a 34-gauge needle. 
     
     
         38 . The syringe of  claim 36 , comprising an 18 to 30-gauge needle. 
     
     
         39 . The syringe of  claim 38 , wherein the device is between 1 mm 3  to 50 mm 3  in size. 
     
     
         40 . The syringe of  claim 36 , wherein the device comprises a live attenuated cancer cell, and wherein 90% or more of the live attenuated cancer cells survive passage of the device through the needle. 
     
     
         41 . The device of  claim 1 , further comprising magnetic particles. 
     
     
         42 . The device of  claim 41 , wherein said magnetic particles comprise Fe 3 O 4  nanoparticles or Fe 3 O 4  micro-particles. 
     
     
         43 . The device of  claim 1 , further comprising mechanophore-molecules. 
     
     
         44 . The device of  claim 43 , wherein said mechanophore molecules comprise polydiacetylene liposomes. 
     
     
         45 . The device of  claim 1 , wherein the cancer comprises melanoma, breast cancer, central nervous system cancer, lung cancer, leukemia, multiple myeloma, renal cancer, malignant glioma, medulloblastoma, colon cancer, stomach cancer, sarcoma, cervical cancer, ovarian cancer, lymphoma, Non-Hodgkin's lymphoma, pancreatic cancer, prostate cancer, thyroid cancer, rectal cancer, endometrial cancer, or bladder cancer.