Background
Immunomodulatory drug delivery
Carrier | Agent | Model system | Outcomea
| References |
---|---|---|---|---|
mPEG-PLGA | Oxaliplatin | Pan02 pancreatic cancer mouse model | Increased TIL levels, increased IFN-γ production | [10] |
Chitosan | IL-12 | MB49 bladder tumor mouse model | Induced antitumoral activity and TH1 cytokine expression | [14] |
Chitosan | IL-12 | MB49 and MBT-2 bladder tumor mouse models | 100% protection to tumor rechallenge in previously cured mice | [15] |
Liposome | Cisplatin CpG | B16–F10 melanoma mouse model | Tumor clearance, long-term protection, Treg downregulation | [31] |
Nanodiamond | CpG | B16–F0 melanoma and 4T1 breast cancer mouse models | IL-12 production and tumor shrinkage | [25] |
PEI | IL-2 plasmid | B16–F1 melanoma mouse model | Reduced tumor growth, prolonged survival, increased TIL tumor infiltration | [18] |
Chitosan | IL-2 plasmid | BALB/c mouse inoculated with WEHI-164 in vitro transfected cells | Tumor mass volume decrease | [162] |
Hydroxyethyl starch | IL-2 | C57BL/6 mouse model; Rag2−/−γc−/− mice reconstituted with human CD4+ T cells | In vivo T cell specific uptake | [20] |
Nanolipogel | IL-2 and TGF-β inhibitor | B16-F10 melanoma mouse model | Increased survival Increased CD8+ T cells tumor infiltration | [19] |
Polylactic acid | IL-12, IL-18, TNF-α alone or in combinations | 4T1 breast cancer mouse models | IL-12 and TNF-α combination was the best condition for controlling tumor growth | [163] |
PLGA-PEI | CpG, IL-10 siRNA | A20 B-cell lymphoma mouse model | Improved TH1/TH2 cytokine expression ratio, Increased survival | [22] |
HA PLGA PLGA | Paclitaxel CpG IL-10 siRNA | B16–F10 melanoma mouse model | Tumor growth inhibition High TH1/TH2 cytokine expression ratio | [32] |
PPS | CpG | E.G7-OVA and B16F10 mouse model | Enhanced TH1 cytokine secretion and protection to tumor rechallenge | [26] |
silica | GM-CSF | In vitro | Increased macrophage proliferation | [24] |
Zinc oxide | Poly I:C | B16–F10 mouse melanoma model | suppressed tumor cell growth | [28] |
PS | Poly I:C | C57BL/6 mouse model | High IL6 production; tnfa, il15, il18, mip3a, and ip10 mRNA upregulation | [164] |
PLGA | Paclitaxel LPS | B16–F10 mouse melanoma model | Increased TIL levels and tumor regression | [33] |
Pyridyl disulfide | Paclitaxel or CpG | B16–F10 mouse melanoma model | Slowed tumor growth, increased CD8+/CD4+ T cell ratio | [27] |
Albumin | Paclitaxel | Phase I studies | Combination with IL-2, IFN-α, cisplatin and temozolomide was too toxic; combination with atezolizumab was well tolerated | |
Liposome | DOX | Phase I study | Combination with IL-18 is safe and biologically active | [55] |
PEG-liposome | DOX | Phase I study | Functional IL-6R blocking with tocilizumab is feasible and safe in combination with PEG-liposomal DOX | [56] |
Adoptive T cell therapy
Cancer vaccines
Carrier | Loaded with | Study type | Outcomea
| References |
---|---|---|---|---|
Liposome | Hsp70 peptide complex | Breast cancer mouse model | Enhanced immune response | [165] |
Liposome | MUC1 peptide, TLR4 ligand | Phase I–II–III studies | Phase I studies: vaccine was well tolerated; phase II study in NSCLC: survival improvement; Phase III study in NSCLC: only improvement observed was in concurrent chemoradiotherapy with a 10.2 month improvement in median survival | |
Liposome | HLA-B7 and β2-microglobulin DNA | Phase II-III studies | Phase II study in metastatic melanoma had a positive outcome, but phase III study failed and product is currently discontinued | |
Liposome | NY-ESO-1, MAGE-A3, tyrosinase and TPTE RNA | Phase I study | Positive outcome in all 3 patients tested. Recruitment of more patients is currently undergoing | [98] |
Liposome | Mix of different peptides | Phase I study | Phase I trial positive outcome, with induced de novo and specific T cell response | |
Liposome | SOCS1, A20 siRNA | Mouse lymphoma model | Drastic enhancement in cytokine production resulting in significant tumor suppression | [166] |
Liposome | E7 HPV | TC-1 lung mouse model | Induced specific CD8+T cell response and Treg inhibition | [167] |
Liposome | OVA, TLR3/9 ligands | C57BL/6 mouse model | Increased CD8+ T cell response | [123] |
γ-PGA/Polylysine | Empty or ovalbumin | C57BL/6 mouse model | Comparative study: PGA has intrinsic immunogenic properties and induced a stronger immune response than polylysine when both loaded with ovalbumin | [160] |
γ-PGA | Ovalbumin | C57BL/6 mouse model | γ-PGA immunogenic properties are TLR4 signalling-dependent | [168] |
Cationic polymers (PE/C32) | CD40 ligand DNA, CpG + poly(I:C) | B16-F10 melanoma mouse model | Comparative study: C32 polimer was superior to PE. TLR ligands had a synergistic effect in triggering immune response | [124] |
PLGA | WTL | In vitro | Co-culture of patient TILs with patient DCs pulsed with autologous WTL-NPs resulted in higher IFN-γ and lower IL-10 production compared to soluble WTL | |
PLGA | WTL, CpG, polyI:C | TRAMP mouse model | Induced CTL response and tumor shrinkage | [112] |
PLGA | WTL | In vitro | Increased T cell proliferation | [113] |
PLGA | Ovalbumin TLR3/7 ligands; CD40, CD11c, or DEC-205 ab | C57BL/6 mouse model | NP coating with targeting molecules (CD40, CD11c or DEC-205 antibodies) induced a stronger immune response | [106] |
PLGA | Ovalbumin, mannose | C57BL/6 mouse model | Decoration of ovalbumin-NPs with mannose moieties increased the efficiency of ovalbumin-specific CD4+ and CD8+ T cell responses | [107] |
PLGA | TRP2180–188; TLR-4 ligand | B16-F10 melanoma mouse model | Immune stimulation in the tumor microenvironment, induction of antigen-specific CD8+ response | [108] |
PLGA | Hgp10025–33 TRP2180–188
| C57BL/6 mouse model | Increased antigen-specific T cell response | [109] |
Cholesteryl pullulan | HER2 fragment; NY-ESO-1 protein | Phase I studies | Vaccine was well tolerated and induced antigen-specific immune responses | |
Chitosan | Ovalbumin, alginate | In vitro | Sugar-coated NP induced higher IFN-γ production in co-culture assays | [169] |
Chitosan | WTL, mannose | B16 melanoma mouse model | Increased tumor growth inhibition | [117] |
BSA/pyridine | Ovalbumin | In vitro | This type of nanogel had intrinsic adjuvant properties | [170] |
Nanogel | Ovalbumin, galactose | B16-OVA mouse model | (pH-sensitive system) cytosolic antigen release; ROS production and increased MHC-I antigen presentation | [133] |