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1. WO2018045058 - DRUG DELIVERY COMPOSITIONS AND USES THEREOF

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Claims

What is claimed is:

1. A drug delivery composition comprising a biomaterial and an activator of innate immune response.

2. A drug delivery composition comprising a biomaterial, an activator of innate immune response, and a cytokine.

3. A drug delivery composition comprising a biomaterial, an activator of innate immune response, and an activator of adaptive immune response.

4. A drug delivery composition comprising a biomaterial and a cytokine.

5. A drug delivery composition comprising a biomaterial, an activator of innate immune response, a cytokine, and an activator of adaptive immune response.

6. A drug delivery composition comprising a biomaterial and an activator of adaptive immune response.

7. A drug delivery composition comprising a biomaterial, a cytokine, and an activator of adaptive immune response.

8. The drug delivery composition of claim 1, wherein the composition comprises a hydrogel and a stimulator of interferon genes (STING) agonist.

9. The drug delivery composition of claim 1, wherein the composition comprises a hydrogel and a TLR7 and/or TLR8 agonist.

10. The drug delivery composition of claim 1, wherein the composition comprises a hydrogel and a TLR7 agonist.

11. The drug delivery composition of claim 1, wherein the composition comprises a hydrogel and a TLR8 agonist.

12. The drug delivery composition of claim 1, wherein the composition comprises a hydrogel and an NLR agonist.

13. The drug delivery composition of claim 4, wherein the composition comprises a hydrogel and an IL-15 superagonist.

14. The drug delivery composition of any one of claims 1, 2, or 4, wherein the composition comprises a hydrogel, a stimulator of interferon genes (STING) agonist, and an IL-15 superagonist.

15. The drug delivery composition of any one of claims 1, 2, or 4, wherein the composition comprises a hydrogel, a TLR7 and/or TLR8 agonist, and an IL-15 superagonist.

16. The drug delivery composition of any one of claims 1, 3, or 6, wherein the composition comprises a hydrogel, a stimulator of interferon genes (STING) agonist, and an anti-PD-1 antibody.

17. The drug delivery composition of any one of claims 1, 3, or 6, wherein the composition comprises a hydrogel, a stimulator of interferon genes (STING) agonist, and an agonist anti-CD 137 antibody.

18. The drug delivery composition of any one of claims 1-7, wherein the composition comprises a hydrogel, a stimulator of interferon genes (STING) agonist, an IL-15 superagonist, and an anti-PD-1 antibody.

19. The drug delivery composition of any one of claims 1-7, wherein the composition comprises a hydrogel, a stimulator of interferon genes (STING) agonist, an IL-15 superagonist, and an agonist anti-CD 137 antibody.

20. The drug delivery composition of any one of claims 1-7, wherein the composition comprises a hydrogel, a TLR7 and/or TLR8 agonist, an IL-15 superagonist, and an anti-PD-1 antibody.

21. The drug delivery composition of any one of claims 1-7, wherein the composition comprises a hydrogel, a TLR3 agonist, an IL-15 superagonist, and an anti-PD-1 antibody.

22. The drug delivery composition of any one of claims 1-7, wherein the composition comprises a hydrogel, a TLR7 and/or TLR8 agonist, an IL-15 superagonist, and an agonist anti-CD 137 antibody.

23. The drug delivery composition of any one of claims 1, 3, or 6, wherein the composition comprises a hydrogel, a stimulator of interferon genes (STING) agonist, an anti-CTLA-4 antibody, and an anti-PD-1 antibody.

24. The drug delivery composition of any one of claims 1, 3, or 6, wherein the composition comprises a hydrogel, a stimulator of interferon genes (STING) agonist, and an anti-CTLA-4 antibody.

25. The drug delivery composition of any one of claims 1, 3, or 6, wherein the composition comprises a hydrogel, a stimulator of interferon genes (STING) agonist, an anti-LAG-3 antibody, and an anti-PD-1 antibody.

26. The drug delivery composition of any one of claims 1-7, wherein the composition comprises a hydrogel, a stimulator of interferon genes (STING) agonist, an IL-15 superagonist, and an anti-LAG-3 antibody.

27. The drug delivery composition of any one of claims 1, 3, or 6, wherein the composition comprises a hydrogel, a TLR7 and/or TLR8 agonist, and an anti-PD-1 antibody.

28. The drug delivery composition of any one of claims 1, 3, or 6, wherein the composition comprises a hydrogel, a TLR7 and/or TLR8 agonist, and an agonist anti-CD 137 antibody.

29. The drug delivery composition of any one of claims 1, 2, or 4, wherein the composition comprises a hydrogel, an NLR agonist, and an IL-15 superagonist.

30. The drug delivery composition of any one of claims 1, 3, or 6, wherein the composition comprises a hydrogel, an NLR agonist, and an anti-CTLA-4 antibody.

31. The drug delivery composition of any one of claims 1, 3, or 6, wherein the composition comprises a hydrogel, a TLR7 and/or TLR8 agonist, an anti-CTLA-4 antibody, and an anti-PD-1 antibody.

32. The drug delivery composition of any one of claims 1, 3, or 6, wherein the composition comprises a hydrogel, a TLR7 and/or TLR8 agonist, and an anti-CTLA-4 antibody.

33. The drug delivery composition of any one of claims 1, 3, or 6, wherein the composition comprises a hydrogel, a TLR7 and/or TLR8 agonist, an anti-LAG-3 antibody, and an anti-PD-1 antibody.

34. The drug delivery composition of any one of claims 1-7, wherein the composition comprises a hydrogel, a TLR7 and/or TLR8 agonist, an IL-15 superagonist, and an anti-LAG-3 antibody.

35. The drug delivery composition of any one of claims 1, 3, or 6, wherein the composition comprises a hydrogel, a STING agonist, an agonist anti-CD 137 antibody, and an anti-CTLA-4 antibody.

36. The drug delivery composition of any one of claims 1, 3, or 6, wherein the composition comprises a hydrogel, a TLR7 and/or TLR8 agonist, an agonist anti-CD 137 antibody, and an anti-CTLA-4 antibody.

37. The drug delivery composition of any one of claims 1, 3, or 6, wherein the composition comprises a hydrogel, a STING agonist, an agonist anti-CD 137 antibody, and an anti-PD-1 antibody.

38. The drug delivery composition of any one of claims 1, 3, or 6, wherein the composition comprises a hydrogel, a TLR7 and/or TLR8 agonist, an agonist anti-CD 137 antibody, and an anti-PD-1 antibody.

39. The drug delivery composition of claim 6, wherein the composition comprises a hydrogel and an agonist anti-CD 137 antibody.

40. The drug delivery composition of claim 6, wherein the composition comprises a hydrogel and an anti-CTLA-4 antibody.

41. The drug delivery composition of claim 6, wherein the composition comprises a hydrogel and an anti-PD-1 antibody.

42. The drug delivery composition of claim 6, wherein the composition comprises a hydrogel, agonist anti-CD 137 antibody, and an anti-PD-1 antibody.

43. The drug delivery composition of claim 6, wherein the composition comprises a hydrogel, agonist anti-CD 137 antibody, and an anti-CTLA-4 antibody.

44. The drug delivery composition of claim 6, wherein the composition comprises a hydrogel, anti-PD-1 antibody, and an anti-CTLA-4 antibody.

45. The drug delivery composition of claim 6, wherein the composition comprises a hydrogel, an agonist anti-CD 137 antibody, an anti-PD-1 antibody, and an anti-CTLA-4 antibody.

46. The drug delivery composition of any one of claims 1-7, wherein the bio material comprises hyaluronic acid, alginate, chitosan, chitin, chondroitin sulfate, dextran, gelatin, collagen, starch, cellulose, polysaccharide, fibrin, ethylene-vinyl acetate (EVA), poly(lactic-co-glycolic) acid (PLGA), polylactic acid (PLA), polyglycolic acid (PGA), polyethylene glycol (PEG), PEG diacrylate (PEGDA), disulfide-containing PEGDA (PEGSSDA), PEG

dimethacrylate (PEGDMA), polydioxanone (PDO), polyhydroxybutyrate (PHB), poly(2-hydroxyethyl methacrylate) (pHEMA), polycaprolactone (PCL), poly (beta- amino ester) (PBAE), poly(ester amide), poly(propylene glycol) (PPG), poly(aspartic acid), poly(glutamic acid), poly(propylene fumarate) (PPF), poly(sebacic anhydride) (PSA), poly(trimethylene carbonate) (PTMC), poly(desaminotyrosyltyrosine alkyl ester carbonate) (PDTE),

poly[bis(trifluoroethoxy)phosphazene], polyoxymethylene, single-wall carbon nanotubes, polyphosphazene, polyanhydride, poly(N-vinyl-2-pyrrolidone) (PVP), poly(vinyl alcohol) (PVA), poly(acrylic acid) (PAA), poly(methacrylic acid) (PMA), polyacetal, poly(alpha ester), poly(ortho ester), polyphosphoester, polyurethane, polycarbonate, polyamide,

polyhydroxyalkanoate, derivatives thereof, or a combination thereof.

47. The drug delivery composition of any one of claims 1-7, wherein the bio material is a hydrogel.

48. The drug delivery composition of any one of claims 8-45 or 47, wherein the hydrogel comprises hyaluronic acid.

49. The drug delivery composition of claim 48, wherein the hyaluronic acid comprises thiol-modified hyaluronic acid and a cross-linking agent.

50. The drug delivery composition of any one of claims 8-45 or 47, wherein the hydrogel comprises alginate.

51. The drug delivery composition of any one of claims 8-45 or 47, wherein the hydrogel comprises a cross-linked biologic.

52. The drug delivery composition of any one of claims 8-45 or 47, wherein the hydrogel comprises a small molecule.

53. The drug delivery composition of claim 4, 6, or 7 further comprising an activator of innate immune response.

54. The drug delivery composition of any one of claims 1-3, 5, or 53, wherein the activator of innate immune response is an effective inducer of type I interferon.

55. The drug delivery composition of any one of claims 1-3, 5, or 53, wherein the activator of innate immune response is a stimulator of interferon genes (STING) agonist, a cytosolic DNA sensor (CDS) agonist, a Toll-like receptor (TLR) agonist, a C-type lectin receptor (CLR) agonist, a NOD-like receptor (NLR) agonist, a RIG-I-like receptor (RLR) agonist, or an inflammasome inducer.

56. The drug delivery composition of any one of claims 1-3, 5, or 53, wherein the activator of innate immune response is 3'3 '-cGAMP, 2'3'-cGAMP, 2'3'-cGAM(PS)2 (Rp Rp), 23'-cGAM(PS)2 (Rp/Sp), 2'2'-cGAMP, c-di-AMP, 2'3 '-c-di-AMP, 2'3 '-c-di-AMP(PS)2 (Rp/Rp), 2'3'-c-di-AMP(PS)2 (Rp/Sp), c-di-GMP, c-di-IMP, HSV-60, ISD, VACV-70, poly(dA:dT), poly(dG:dC), heat-killed bacteria, lipoglycans, lipopolysaccharides (LPS), lipoteichoic acids, peptidoglycans (PGNs), synthetic lipoproteins, poly(A:U), poly(LC), Monophosphoryl Lipid A (MPLA), GSK1795091, GlOO, SD-101, MGN1703, CMP-001, flagellin (FLA), polyU, poly(dT), gardiquimod, imiquimod (R837), base analogs, adenine analogs, guanosin analogs, purine derivatives, benoazepine analogs, xanthenone analogs, imidazoquinolines, thiazoquinolines, loxoribine, resiquimod (R848), dactolisib, sumanirole, R837, Nl-glycinyl[4-((6-amino-2-(butylamino)-8-hydroxy-9H-purin-9-yl)methyl) benzoyl] spermine (CL307), CL264, CL097, CL075, MEDI9197, MEDI5083, hypoxanthine, TL8-506, PF-4878691, isatoribine, SM-324405, SM-324406, AZ12441970, AZ12443988, CpG oligonucleotides, bacterial DNA, beta glucans,

beta glucans from fungal and bacterial cell walls, γ-D-Glu-mDAP (iE-DAP), iE-DAP derivatives, muramyl dipeptide (MDP), MDP derivatives, 5' triphosphate double stranded RNA,

poly(dA:dT), ATP, chitosan, aluminum potassium sulfate, calcium pyrophosphate dehydrate, silica dioxide, a derivative thereof, or a pharmaceutically acceptable salt thereof.

57. The drug delivery composition of any one of claims 1-3, 5, or 53, wherein the activator of innate immune response is 3'3 '-cGAMP, 2'3'-cGAMP, 2'3'-cGAM(PS)2 (Rp Rp), 23'-cGAM(PS)2 (Rp/Sp), 2'2'-cGAMP, c-di-AMP, 23 '-c-di-AMP, 2'3 '-c-di-AMP(PS)2 (Rp/Rp), 2'3'-c-di-AMP(PS)2 (Rp/Sp), c-di-GMP, c-di-IMP, HSV-60, ISD, VACV-70, poly(dA:dT), poly(dG:dC), heat-killed bacteria, lipoglycans, lipopolysaccharides (LPS), lipoteichoic acids, peptidoglycans (PGNs), synthetic lipoproteins, poly(A:U), poly(LC), Monophosphoryl Lipid A (MPLA), flagellin (FLA), polyU, poly(dT), gardiquimod, imiquimod, loxoribine, resiquimod (R848), CpG oligonucleotides, bacterial DNA, beta glucans, beta glucans from fungal and bacterial cell walls, γ-D-Glu-mDAP (iE-DAP), iE-DAP derivatives, muramyl dipeptide (MDP), MDP derivatives, 5' triphosphate double stranded RNA, poly(dA:dT), ATP, chitosan, aluminum potassium sulfate, calcium pyrophosphate dehydrate, silica dioxide, poly(dA:dT), FLA, MDP, MurNAc-L-Ala-y-D-Glu-mDAP (M-TriDAP), a derivative thereof, or a pharmaceutically acceptable salt thereof.

58. The drug delivery composition of any one of claims 1-3, 5, or 53, wherein the activator of innate immune response is 3'3 '-cGAMP, 2'3 '-cGAMP, 2'3'-cGAM(PS)2 (Rp,Rp), 23'-cGAM(PS)2 (Rp,Sp), 2'2'-cGAMP, c-di-AMP, 23 '-c-di-AMP, 2'3'-c-di-AM(PS)2 (Rp,Rp), 2'3'-c-di-AM(PS)2 (Rp,Sp), c-di-GMP, 23 '-c-di-GMP, 2'3'-c-di-GM(PS)2 (Rp,Rp), 2'3'-c-di-GM(PS)2 (Rp,Sp), c-di-IMP, resiquimod, a CpG oligonucleotide, polyinosinic:polycytidylic acid, a fluorinated derivative thereof, an O-methylated derivative thereof, or a pharmaceutically acceptable salt thereof.

59. The drug delivery composition of any one of claims 1-3, 5, or 53, wherein the activator of innate immune response is 2'3 '-cGAMP, or a pharmaceutically acceptable salt thereof.

60. The drug delivery composition of any one of claims 1-3, 5, or 53, wherein the activator of innate immune response is 2 '-c-di-AM(PS)2 (Rp,Rp), or a pharmaceutically acceptable salt thereof.

61. The drug delivery composition of any one of claims 1-3, 5, or 53, wherein the activator of innate immune response is a cyclic dinucleotide.

62. The drug delivery composition of any one of claims 1-3, 5, or 53, wherein the activator of innate immune response is a cGAS agonist.

63. The drug delivery composition of any one of claims 1-3, 5, or 53, wherein the activator of innate immune response is a TREX1 inhibitor.

64. The drug delivery composition of any one of claims 1-3, 5, or 53, wherein the activator of innate immune response is resiquimod, or a pharmaceutically acceptable salt thereof.

65. The drug delivery composition of any one of claims 1-3, 5, or 53, wherein the activator of innate immune response is MurNAc-L-Ala-y-D-Glu-mDAP (M-TriDAP), or a pharmaceutically acceptable salt thereof.

66. The drug delivery composition of any one of claims 1-3, 5, or 53, wherein the activator of innate immune response is an imidazoquinoline.

67. The drug delivery composition of any one of claims 2, 4, 5, or 7, wherein the cytokine is IL-1, IL-la, IL-Ιβ, IL-2, an IL-2 superkine, IL-6, IL-7, IL-9, AMOOIO, IL-12, IL-15, an IL-15 superagonist, ALT-803, NIZ985, IL-16, IL-18, IL-21, denenicokin, an IL-21 superagonist antibody, IFN-a, IFN-β, IFN-γ, TNF-a, GM-CSF, a cytokine fusion, RG7461, RG7813, or M9241.

68. The drug delivery composition of any one of claims 2, 4, 5, or 7, wherein the cytokine is a chemokine, wherein the chemokine is CCLl, CCL2, CCL3, CCL4, CCL5, CCL17, CCL19, CCL21, CCL22, CXCL9, CXCL10, CXCL11, CXCL13, CXCL16, or CX3CL1.

69. The drug delivery composition of any one of claims 2, 4, 5, or 7, wherein the cytokine is an IL-15 superagonist.

70. The drug delivery composition of any one of claims 2, 4, 5, or 7, wherein the cytokine is interferon a (IFN-a).

71. The drug delivery composition of any one of claims 2, 4, 5, or 7, wherein the cytokine is interferon β (IFN-β).

72. The drug delivery composition of any one of claims 2, 4, 5, or 7, wherein the cytokine is interferon γ (IFN-γ).

73. The drug delivery composition of any one of claims 2, 4, 5, or 7, wherein the cytokine is IL-Ιβ.

74. The drug delivery composition of any one of claims 1-3, 5, or 53 further comprising an additional activator of innate immune response.

75. The drug delivery composition of any one of claims 1, 2, or 4 further comprising an activator of adaptive immune response.

76. The drug delivery composition of any one of claims 3, 5-7, or 75, wherein the activator of adaptive immune response is a biologic.

77. The drug delivery composition of any one of claims 3, 5-7, 75, or 76, wherein the activator of adaptive immune response is a protein.

78. The drug delivery composition of any one of claims 3, 5-7, 75 or 76, wherein the activator of adaptive immune response is a nucleic acid that encodes a protein.

79. The drug delivery composition of any one of claims 3, 5-7, or 75-77, wherein the activator of adaptive immune response is an anti-PD-1 antibody, an anti-PD-Ll antibody, an anti-CTLA-4 antibody, an anti-TIM3 antibody, an anti-OX40 antibody, an anti-GITR antibody, an anti-LAG-3 antibody, an anti-CD 137 antibody, an anti-CD27 antibody, an anti-CD28 antibody, an anti-CD28H antibody, an anti-CD30 antibody, an anti-CD39 antibody, an anti-CD40 antibody, an anti-CD47 antibody, an anti-CD48 antibody, an anti-CD70 antibody, an anti-CD73 antibody, an anti-CD96 antibody, an anti-CD 160 antibody, an anti-CD200 antibody, an anti-CD244 antibody, an anti-ICOS antibody, an anti-TNFRSF25 antibody, an anti-TMIGD2 antibody, an anti-DNAMl antibody, an anti-BTLA antibody, an anti-LIGHT antibody, an anti-TIGIT antibody, an anti- VISTA antibody, an anti-HVEM antibody, an anti-Siglec antibody, an anti-GALl antibody, an anti-GAL3 antibody, an anti-GAL9 antibody, an anti-BTNL2

(butrophylins) antibody, an anti-B7-H3 antibody, an anti-B7-H4 antibody, an anti-B7-H5 antibody, an anti-B7-H6 antibody, an anti-KIR antibody, an anti-LIR antibody, an anti-ILT antibody, an anti-MICA antibody, an anti-MICB antibody, an anti-NKG2D antibody, an anti-NKG2A antibody, an anti-TGFp antibody, an anti-TGFpR antibody, an anti-CXCR4 antibody, an anti-CXCL12 antibody, an anti-CCL2 antibody, an anti-IL-10 antibody, an anti-IL-13 antibody, an anti-IL-23 antibody, an anti-phosphatidylserine antibody, an anti-neuropilin antibody, an anti-GalCer antibody, an anti-HER2 antibody, an anti-VEGFA antibody, an anti-VEGFR antibody, an anti-EGFR antibody, an anti-Tie2 antibody, or antibody fragments thereof.

80. The drug delivery composition of any one of claims 3, 5-7, or 75-77, wherein the activator of adaptive immune response is an anti-PD-1 antibody, an anti-PD-Ll antibody, an anti-CTLA-4 antibody, an anti-TIM3 antibody, an anti-OX40 antibody, an anti-GITR antibody, an anti-LAG-3 antibody, an anti-CD 137 antibody, an anti-CD27 antibody, an anti-CD28 antibody, an anti-CD28H antibody, an anti-CD30 antibody, an anti-CD39 antibody, an anti-CD40 antibody, an anti-CD47 antibody, an anti-CD48 antibody, an anti-CD70 antibody, an anti-CD73 antibody, an anti-CD96 antibody, an anti-CD 155 antibody, an anti-CD 160 antibody, an anti-CD200 antibody, an anti-CD244 antibody, an anti-ICOS antibody, an anti-TNFRSF25

antibody, an anti-TMIGD2 antibody, an anti-DNAMl antibody, an anti-BTLA antibody, an anti-LIGHT antibody, an anti-TIGIT antibody, an anti- VISTA antibody, an anti-HVEM antibody, an anti-Siglec antibody, an anti-GALl antibody, an anti-GAL3 antibody, an anti-GAL9 antibody, an anti-BTNL2 (butrophylins) antibody, an anti-B7-H3 antibody, an anti-B7-H4 antibody, an anti-B7-H5 antibody, an anti-B7-H6 antibody, an anti-KIR antibody, an anti-LIR antibody, an anti-ILT antibody, an anti-MICA antibody, an anti-MICB antibody, an anti-NKG2D antibody, an anti-NKG2A antibody, an anti-A2AR antibody, an anti-C5aR antibody, an anti-TGFp antibody, an anti-TGFpR antibody, an anti-CXCR4 antibody, an anti-CXCL12 antibody, an anti-CCL2 antibody, an anti-IL-10 antibody, an anti-IL-13 antibody, an anti-IL-23 antibody, an anti-phosphatidylserine antibody, an anti-neuropilin antibody, an anti-GalCer antibody, an anti-HER2 antibody, an anti-VEGFA antibody, an anti-VEGFR antibody, an anti-EGFR antibody, an anti-Tie2 antibody, an anti-CCR4 antibody, an anti-TRAIL-DR5 antibody, an anti-CD3 antibody, an anti-CD43 antibody, an anti-CD 123 antibody, an anti-CEACAMl antibody, an anti-CEACAM5 antibody, an anti-CEACAM6 antibody, or antibody fragments thereof.

81. The drug delivery composition of any one of claims 3, 5-7, or 75-77, wherein the activator of adaptive immune response is an anti-PD-1 antibody.

82. The drug delivery composition of any one of claims 3, 5-7, or 75-77, wherein the activator of adaptive immune response is an agonist anti-CD 137 antibody.

83. The drug delivery composition of any one of claims 3, 5-7, or 75-77, wherein the activator of adaptive immune response is an anti-CTLA-4 antibody.

84. The drug delivery composition of any one of claims 3, 5-7, or 75-77, wherein the activator of adaptive immune response is pembrolizumab, nivolumab, pidilizumab, ipilimumab, tremelimumab, durvalumab, atezolizumab, avelumab, PF-06801591, utomilumab, PDR001, PBF-509, MGB453, LAG525, AMP-224, INCSHR1210, INCAGN1876, INCAGN1949, samalizumab, PF-05082566, urelumab, lirilumab, lulizumab, BMS-936559, BMS-936561, BMS-986004, BMS-986012, BMS-986016, BMS-986178, IMP321, IPH2101, IPH2201, varlilumab, ulocuplumab, monalizumab, MEDI0562, MEDI0680, MEDI1873, MEDI6383, MEDI6469,

MEDI9447, AMG228, AMG820, CC-90002, CDX-1127, CGEN15001T, CGEN15022,

CGEN15029, CGEN15049, CGEN15027, CGEN15052, CGEN15092, CX-072, CX-2009, CP-870893, lucatumumab, dacetuzumab, Chi Lob 7/4, RG6058, RG7686, RG7876, RG7888, TRX518, MK-4166, IMC-CS4, emactuzumab, trastuzumab, pertuzumab, obinutuzumab, cabiralizumab, margetuximab, enoblituzumab, mogamulizumab, panitumumab, carlumab, bevacizumab, rituximab, or cetuximab.

85. The drug delivery composition of any one of claims 3, 5-7, or 75-77, wherein the activator of adaptive immune response is pembrolizumab, nivolumab, pidilizumab, ipilimumab, tremelimumab, durvalumab, atezolizumab, avelumab, PF-06801591, utomilumab, PDR001, PBF-509, MGB453, LAG525, AMP-224, INCSHR1210, INCAGN1876, INCAGN1949, samalizumab, PF-05082566, urelumab, lirilumab, lulizumab, BMS-936559, BMS-936561, BMS-986004, BMS-986012, BMS-986016, BMS-986178, IMP321, IPH2101, IPH2201, IPH5401, IPH4102, IPH4301, IPH52, IPH53, varlilumab, ulocuplumab, monalizumab, MEDI0562, MEDI0680, MEDI1873, MEDI6383, MEDI6469, MEDI9447, AMG228, AMG820, CC-90002, CDX-1127, CGEN15001T, CGEN15022, CGEN15029, CGEN15049, CGEN15027,

CGEN 15052, CGEN 15092, CX-072, CX-2009, CP-870893, lucatumumab, dacetuzumab, Chi Lob 7/4, RG6058, RG7686, RG7876, RG7888, TRX518, MK-4166, IMC-CS4, emactuzumab, trastuzumab, pertuzumab, obinutuzumab, cabiralizumab, margetuximab, enoblituzumab, mogamulizumab, panitumumab, carlumab, ramucirumab, bevacizumab, rituximab, cetuximab, fresolimumab, denosumab, MGA012, AGEN1884, AGEN2034, LY3300054, JTX-4014, teplizumab, FPA150, PF-04136309, PF-06747143, AZD5069, GSK3359609, FAZ053, TSR022, MBG453, REGN3767, REGN2810, GSK3174998, MOXR0916, PF-04518600, RO7009789, BMS986156, GWN323, JTX-2011, NKTR-214, DS-8273a, NIS793, or BGB-A317.

86. The drug delivery composition of any one of claims 3, 5-7, or 75-77, wherein the activator of adaptive immune response is a bispecific antibody.

87. The drug delivery composition of claim 86, wherein the bispecific antibody is RG7802, RG7828, RG7221, RG7386, ERY974, MGD012, AMG211, MEDI573, MEDI565, FS 17, FS 18, FS20, FS22, FS 101, FS 117, FS 118, R06958688, MCLA-128, M7824, MGD009, or MGD013.

88. The drug delivery composition of any one of claims 3, 5-7, or 75-77 wherein the activator of adaptive immune response is an antibody-drug conjugate.

89. The drug delivery composition of claim 88, wherein the antibody-drug conjugate is trastuzumab emtansine, inotuzumab ozogamicin, PF-06647020, PF-06647263, PF-06650808, RG7596, RG7841, RG7882, RG7986, DS-8201, ABBV-399, glembatumumab vedotin, inotuzumab ozogamicin, MEDI4276, or a pharmaceutically acceptable salt thereof.

90. The drug delivery composition of claim 3, 5-7, or 75, wherein the activator of adaptive immune response is a small molecule.

91. The drug delivery composition of claim 90, wherein the small molecule is an IDO inhibitor, a TGFP inhibitor, a BRAF inhibitor, a KIT inhibitor, an A2aR inhibitor, a Tie2 inhibitor, an arginase inhibitor, an iNOS inhibitor, an HIFla inhibitor, a STAT3 inhibitor, a PGE2 inhibitor, a PDE5 inhibitor, a RON inhibitor, an mTOR inhibitor, a JAK2 inhibitor, a HSP90 inhibitor, a PI3K-AKT inhibitor, a WNT-p-catenin inhibitor, a GSK3p inhibitor, an IAP inhibitor, an HDAC inhibitor, a DNMT inhibitor, a BET inhibitor, a COX2 inhibitor, a PDGFR inhibitor, a VEGFR inhibitor, a BCR-ABL inhibitor, a proteasome inhibitor, an angiogenesis inhibitor, celecoxib, sunitinib, imatinib, vemurafenib, dabrafenib, bortezomib, vorinostat, pomalidomide, thalidomide, lenalidomide, or a pharmaceutically acceptable salt thereof.

92. The drug delivery composition of claim 90, wherein the small molecule is an IDO inhibitor, a TGFpR inhibitor, a BRAF inhibitor, a KIT inhibitor, an A2aR inhibitor, a Tie2 inhibitor, an arginase inhibitor, an iNOS inhibitor, an HIFla inhibitor, a STAT3 inhibitor, a PGE2 inhibitor, a PDE5 inhibitor, a RON inhibitor, an mTOR inhibitor, a JAK2 inhibitor, a HSP90 inhibitor, a PI3K-AKT inhibitor, a WNT-p-catenin inhibitor, a GSK3p inhibitor, an IAP inhibitor, an HDAC inhibitor, a DNMT inhibitor, a BET inhibitor, a COX2 inhibitor, a PDGFR inhibitor, a VEGFR inhibitor, a BCR-ABL inhibitor, an FGFR3 inhibitor, a proteasome inhibitor, an angiogenesis inhibitor, a MEK inhibitor, a BRAF + MEK inhibitor, a pan-RAF inhibitor, an EGFR inhibitor, a PARP inhibitor, a glutaminase inhibitor, a FAK inhibitor, an ALK inhibitor, a CDK4/6 inhibitor, a WNT inhibitor, celecoxib, sunitinib, imatinib, vemurafenib, dabrafenib, bortezomib, vorinostat, pomalidomide, thalidomide, lenalidomide, epacadostat, indoximid, GDC0919, BMS986205, AZD8055, AZD4635, CPI-444, PBF509, LCL161, CB-839, CB-1158, FPA008, BLZ945, IPI-549, pexidartinib, galunisertib, birinapant, trametinib, cobimetinib, binimetinib, ensartib, gefitinib, pazopanib, sorafenib, nintedanib, SYM004, veliparib, olaparib, BGB-290, everolimus, LXH254, azacitidine, decitabine, guadecitabine, RRX001, CC486, romidepsin, entinostat, panobinostat, tamoxifen, ibrutinib, idelalisib, capmatinib, selumetinib, abemaciclib, palbociclib, glasdegib, enzalutamide, AZD9150, PF-06840003, SRF231, Hu5F9-G4, CC-900002, TTI-621, WNT974, BGJ398, or LY2874455, or a pharmaceutically acceptable salt thereof.

93. The drug delivery composition of any one of claims 1-7 further comprising a modulator of macrophage effector function.

94. The drug delivery composition of claim 93, wherein the modulator of macrophage effector function is an anti-CD40 antibody, an anti-CD47 antibody, an anti-CSFl antibody, an anti-CSFIR antibody, or a small molecule inhibitor of CSF1R, BTK, ITK, ΡΒΚγ, or PI3K5.

95. The drug delivery composition of any one of claims 3, 5-7, or 75-94 further comprising an additional activator of adaptive immune response.

96. The drug delivery composition of any one of claims 1-95 further comprising an oncolytic virus, a radioactive isotope, a chemotherapeutic agent, or a combination thereof.

97. The drug delivery composition of any one of claims 1-95 further comprising an oncolytic virus, a radioactive isotope, an immunomodulatory chemotherapeutic agent, a targeted agent, or a combination thereof.

98. The drug delivery composition of any one of claims 1-97 further comprising at least one excipient.

99. The drug delivery composition of claim 98, wherein the excipient is phosphate-buffered saline, tris(hydroxymethyl)aminomethane, sodium chloride, trehalose, sucrose, or a combination thereof.

100. The drug delivery composition of any one of claims 1-99, wherein the composition does not comprise adoptively transferred cells, microparticles, peptides, or tumor antigens loaded ex vivo.

101. The drug delivery composition of any one of claims 1-100, wherein the composition does not comprise an organic solvent.

102. The drug delivery composition of any one of claims 1-98, wherein the composition comprises an organic solvent.

103. A drug delivery composition selected from the group consisting of:

a composition comprising a hydrogel and 2'3'-cGAMP;

a composition comprising a hydrogel and 2'3'-c-di-AM(PS)2 (Rp,Rp);

a composition comprising a hydrogel and resiquimod;

a composition comprising a hydrogel and M-TriDAP;

a composition comprising a hydrogel and an IL-15 superagonist;

a composition comprising a hydrogel and interferon a (IFN- );

a composition comprising a hydrogel and interferon β (IFN-β);

a composition comprising a hydrogel and interferon γ (IFN-γ);

a composition comprising a hydrogel, 2 '-cGAMP, and an IL-15 superagonist;

a composition comprising a hydrogel, 2 '-c-di-AM(PS)2 (Rp,Rp), and an IL-15 superagonist;

a composition comprising a hydrogel, resiquimod, and an IL-15 superagonist;

a composition comprising a hydrogel, 2 '-cGAMP, an IL-15 superagonist, and an anti-PD-1 antibody;

a composition comprising a hydrogel, 2 '-c-di-AM(PS)2 (Rp,Rp), an IL-15 superagonist, and an anti-PD-1 antibody; and

a composition comprising a hydrogel, resiquimod, an IL-15 superagonist, and an anti-PD-1 antibody.

104. The drug delivery composition of any one of claims 8-45, 47, or 103, wherein the hydrogel comprises hyaluronic acid or alginate.

105. A drug delivery device comprising the drug delivery composition of any one of claims 1-104.

106. The drug delivery device of claim 105, wherein the hydrogel comprises cross-linked hyaluronic acid.

107. The drug delivery device of claim 105, wherein the hydrogel comprises cross-linked alginate.

108. The drug delivery device of any one of claims 105-107, wherein the hydrogel is biodegradable in vivo.

109. The drug delivery device of any one of claims 105-108 wherein less than or equal to 20% of the device remains in vivo 6 months after implantation of the device.

110. The drug delivery device of any one of claims 105-109, wherein the device has a storage modulus of at least 100 Pa.

111. The drug delivery device of any one of claims 105-109, wherein the device has a storage modulus of up to 100,000,000 Pa.

112. The drug delivery device of any one of claims 105-109, wherein the device has a storage modulus of about 500 Pa to about 3000 Pa.

113. The drug delivery device of any one of claims 105-112, wherein less than or equal to 80% of the activator of innate immune response is released in vivo 30 minutes after implantation of the composition.

114. The drug delivery device of any one of claims 105-113, wherein less than or equal to 80% of the activator of adaptive immune response is released in vivo 10 hours after implantation of the composition.

115. The drug delivery device of any one of claims 105-114, wherein less than or equal to 80% of the cytokine is released in vivo 10 hours after implantation of the composition.

116. A method of treating cancer in a subject in need thereof, the method comprising surgically implanting the drug delivery device of any one of claims 105-115 in the subject.

117. A method of preventing cancer in a subject in need thereof, the method comprising surgically implanting the drug delivery device of any one of claims 105-115 in the subject.

118. The method of claim 116 or 117, wherein the cancer is a sarcoma, a carcinoma, a lymphoma, a germ cell tumor, or a blastoma.

119. The method of any one of claims 116-118, wherein the cancer is adenocarcinoma, adrenal gland cancer, anal cancer, angiosarcoma, appendix cancer, bile duct cancer, bladder cancer, bone cancer, brain cancer, breast cancer, bronchus cancer, carcinoid tumor, cardiac tumor, cervical cancer, choriocarcinoma, chordoma, colorectal cancer, connective tissue cancer, craniopharyngioma, ductal carcinoma in situ, endotheliosarcoma, endometrial cancer,

ependymoma, epithelial carcinoma, esophageal cancer, Ewing's sarcoma, eye cancer, familiar hypereosinophilia, gall bladder cancer, gastric cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (GIST), germ cell cancer, head and neck cancer,

hemangioblastoma, histiocytosis, Hodgkin lymphoma, hypopharynx cancer, inflammatory myofibroblastic tumors, intraepithelial neoplasms, immunocytic amyloidosis, Kaposi sarcoma, kidney cancer, liver cancer, lung cancer, leiomyosarcoma (LMS), mastocytosis, melanoma,

midline tract carcinoma, multiple endocrine neoplasia syndrome, multiple myeloma, muscle cancer, myelodysplastic syndrome (MDS), mesothelioma, myeloproliferative disorder (MPD), nasopharynx cancer, neuroblastoma, neurofibroma, neuroendocrine cancer, non-Hodgkin lymphoma, osteosarcoma, ovarian cancer, pancreatic cancer, paraneoplastic syndromes, parathryroid cancer, papillary adenocarcinoma, penile cancer, pharyngeal cancer,

pheochromocytoma, pinealoma, pituitary cancer, pleuropulmonary blastoma, primitive neuroectodermal tumor (PNT), plasma cell neoplasia, prostate cancer, rectal cancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, sebaceous gland carcinoma, skin cancer, small bowel cancer, small intestine cancer, soft tissue sarcoma, stomach cancer, sweat gland carcinoma, synovioma, testicular cancer, thymic cancer, thyroid cancer, urethral cancer, uterine cancer, vaginal cancer, vascular cancer, or vulvar cancer.

120. A method of preventing primary tumor regrowth in a subject in need thereof, the method comprising surgically implanting the drug delivery device of any one of claims 105-115 in the subject.

121. A method of preventing tumor metastasis in a subject in need thereof, the method comprising surgically implanting the drug delivery device of any one of claims 105-115 in the subject.

122. The method of claim 120 or 121, wherein the tumor is a sarcoma, a carcinoma, a lymphoma, a germ cell tumor, a blastoma, or a combination thereof.

123. The method of any one of claims 116-122 further comprising implanting the drug delivery device after surgical resection of a tumor.

124. The method of claim 123 further comprising implanting the drug delivery device at the site of tumor resection.

125. The drug delivery device of any one of claims 105-115 for use in the treatment of cancer in a subject in need thereof.

126. The drug delivery device of any one of claims 105-115 for use in the prevention of cancer in a subject in need thereof.

127. The drug delivery device of claim 125 or 126, wherein the cancer is a sarcoma, a carcinoma, a lymphoma, a germ cell tumor, or a blastoma.

128. The drug delivery device of any one of claims 125-127, wherein the cancer is

adenocarcinoma, adrenal gland cancer, anal cancer, angiosarcoma, appendix cancer, bile duct cancer, bladder cancer, bone cancer, brain cancer, breast cancer, bronchus cancer, carcinoid tumor, cardiac tumor, cervical cancer, choriocarcinoma, chordoma, colorectal cancer, connective tissue cancer, craniopharyngioma, ductal carcinoma in situ, endotheliosarcoma, endometrial cancer, ependymoma, epithelial carcinoma, esophageal cancer, Ewing's sarcoma, eye cancer, familiar hypereosinophilia, gall bladder cancer, gastric cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (GIST), germ cell cancer, head and neck cancer,

hemangioblastoma, histiocytosis, Hodgkin lymphoma, hypopharynx cancer, inflammatory myofibroblastic tumors, intraepithelial neoplasms, immunocytic amyloidosis, Kaposi sarcoma, kidney cancer, liver cancer, lung cancer, leiomyosarcoma (LMS), mastocytosis, melanoma, midline tract carcinoma, multiple endocrine neoplasia syndrome, multiple myeloma, muscle cancer, myelodysplastic syndrome (MDS), mesothelioma, myeloproliferative disorder (MPD), nasopharynx cancer, neuroblastoma, neurofibroma, neuroendocrine cancer, non-Hodgkin lymphoma, osteosarcoma, ovarian cancer, pancreatic cancer, paraneoplastic syndromes, parathryroid cancer, papillary adenocarcinoma, penile cancer, pharyngeal cancer,

pheochromocytoma, pinealoma, pituitary cancer, pleuropulmonary blastoma, primitive neuroectodermal tumor (PNT), plasma cell neoplasia, prostate cancer, rectal cancer,

retinoblastoma, rhabdomyosarcoma, salivary gland cancer, sebaceous gland carcinoma, skin cancer, small bowel cancer, small intestine cancer, soft tissue sarcoma, stomach cancer, sweat gland carcinoma, synovioma, testicular cancer, thymic cancer, thyroid cancer, urethral cancer, uterine cancer, vaginal cancer, vascular cancer, or vulvar cancer.

129. The drug delivery device of any one of claims 105-115 for use in the prevention of primary tumor regrowth in a subject in need thereof.

130. The drug delivery device of any one of claims 105-115 for use in the prevention of tumor metastasis in a subject in need thereof.

131. The drug delivery device of claim 129 or 130, wherein the tumor is a sarcoma, a carcinoma, a lymphoma, a germ cell tumor, a blastoma, or a combination thereof.

132. The drug delivery device of any one of claims 105-115 for implantation at a site of tumor resection in a subject in need thereof.

133. A kit comprising a hydrogel and an activator of innate immune response.

134. A kit comprising a hydrogel and a cytokine.

135. A kit comprising a hydrogel and an activator of adaptive immune response.

136. The kit of claim 133 or 135 further comprising a cytokine.

137. The kit of claim 133 or 134 further comprising an activator of adaptive immune response.

138. The kit of any one of claims 133-137 further comprising a modulator of macrophage effector function.

139. The kit of any one of claims 133-138 further comprising an additional activator of adaptive immune response.

140. The kit of any one of claims 133-139 further comprising an additional activator of innate immune response.

141. The kit of any one of claims 133-140 further comprising an oncolytic virus, a radioactive isotope, a chemotherapeutic agent, or a combination thereof.

142. The kit of any one of claims 133-141 further comprising an oncolytic virus, a radioactive isotope, an immunomodulatory chemotherapeutic agent, a targeted agent, or a combination thereof.

143. A kit comprising the drug delivery composition of any one of claims 1-104.

144. A kit comprising the drug delivery device of any one of claims 105-115.