Table 2.
Targeting moiety | Injection | Content | Effect | References |
---|---|---|---|---|
CLR | ||||
| ||||
DEC205
α-GalCer NP |
fp | OVA | ↑iNKT, ↓growth in B16F10, and EG7-OVA (P + T) | [147] |
Selected nucleic acid aptamer | i.v. | OVA | ↑CD8, ↓growth OVA-B16 tumor (T if OT-I transfer) | [95] |
Anti-CD11c and DEC205 scFv coupled to NP | i.v. | OVA + ADJ | ↑CD8, ↓growth OVA-B16 tumor (P) | [83] |
mAb fused protein | s.c. | OVA + ADJ | ↑CD8, ↓growth OVA-B16 (P + T) | [131] |
mAb fused protein | i.p. | HER2 + ADJ | ↑CD8, ↑CD4, ↑humoral, and ↓growth neu-expressing mammary tumor (P) | [148, 149] |
mAb fused protein | i.p. | Mesothelin + ADJ | ↑cross-presentation, ↑CD4, ↑humoral, and ↓growth neu-expressing mammary tumor (P) | [150] |
scFV modified adenoviral vector | fp | OVA | ↑T cell, ↑humoral (at low doses), ↓growth OVA-B16 (P) BUT better for untargeted vectors | [127] |
mAb fused protein | fp | OVA + ADJ | ↑CD8, ↓growth B16 pseudo-metastasis model (P + T) | [120] |
Bacteriophage displaying scFV | fp | OVA | ↓growth B16F10 (Pro + Ther) | [151] |
mAb fused protein | s.c. | Trp2 and gp100 + ADJ | ↑CD8, ↑CD4, and ↓growth B16 melanoma (P + T) | [152] |
scFV fused to DNA vaccine | i.m. | Her2/neu + CPM | ↑CD8, ↑humoral, long lasting memory ↓growth HER2/neu + D2F2/E2 breast tumor + spontaneous mammary carcinomas (P + T) | [153] |
Phase I clinical trial with CDX-1401 = human mAb fused protein | i.d. | NY-ESO-1 + ADJ | Patients with advanced malignancies: ↑cellular, ↑humoral (T) | [154] |
| ||||
DEC206
Mannosylated NP |
s.c. | OVA + ADJ | ↑TH1 cell, ↑humoral, and ↓growth B16F10 (P + T) | [155] |
mAb fused to protein | s.c. | OVA + ADJ | ↑T cell, ↑humoral, and ↓growth B11-OVA (P) | [156] |
Mannan coupled protein | i.p. | MUC-1 | ↑CD8, ↓growth P815 mastocytoma (T) | [157] |
Mannose coupled dendrimer | i.d. | OVA | ↑CD8, ↑CD4, ↑humoral, ↓growth B16-OVA (P) | [158] |
Mannosylated NP | s.c. | ErbB2/HER3 + ADJ | ↓growth huErbB2+ renal carcinoma cells (T) | [125] |
Mannan coated liposome-protamine-DNA | U | HPV16 E7 | ↓growth E7+ TC-1 (P + T) | [159] |
Mannosylated and/or histidylated NP loaded with mRNA | i.v. | MART-1 | ↑CD8, ↓growth B16F10 (P) | [160, 161] |
Mannan or pullulan NP complexed with protein | U | HER2 | ↑CD8, ↓growth HER2+ tumors (P + T) | [162] |
D-mannose conjugated lipid-core peptide system | s.c. | HPV16 E7 | ↓growth TC-1 HPV-16 tumor (P) | [163] |
Clinical trial with mannan coupled protein | s.c. | MUC-1 | ↑humoral, less ↑CD8, protection against recurrence in breast cancer patients | [106] |
Two phase I studies with CDX-1307 = hCG-β fused to mAb | i.d. or i.v. | hCG-β + ADJ | ↑humoral and T cell with clinical benefit in patients with advanced epithelial malignancies | [164] |
DC-SIGN
LV pseudotyped with point-mutated Sindbis virus glycoprotein |
i.d. | OVA or PSCA | ↑CD8, ↑CD4, and ↓growth transgenic adenocarcinoma, E.G7-OVA and PSCA-expressing B16-F10 (P + T) | [5, 103, 165] |
mAb coupled protein | U | KLH | ↓growth human Burkitt's lymphoma cell line in humanized mice (P) | [166] |
IDLV pseudotyped with engineered Sindbis virus glycoprotein + currently tested in Phase I clinical trial ID-VP02 | s.c. | NY-ESO + Vpx | ↑CD8, ↓growth CT26 colon carcinoma cells (P + T) | [167, 168] |
| ||||
LOX-1
HSP70 fused to protein |
s.c. | OVA | ↑CD8 and cross-priming, ↓growth E.G7 cells (P) | [169] |
| ||||
CLEC9A
mAb coupled to peptide |
s.c. | MUC-1 + ADJ | ↑TH1, ↓growth MUC-1-A2K/b+ MC38 (P + T) | [170] |
mAb coupled to peptide | s.c. | OVA + ADJ | ↑CD8, ↓growth B16 lung pseudo metastases (P + T) | [138] |
| ||||
DCIR2
Anti-DCIR2 or anti-DEC205 mAb coupled protein |
i.p. | OVA + ADJ | ↑CD8, ↑CD4 (mixed TH1/TH2), ↑humoral, and ↓growth B16F10-OVA (P + T) | [171] |
| ||||
Integrin | ||||
| ||||
CD11c
Targeted lipopeptide |
i.d. | OVA, WT1, tumor lysate + ADJ | ↓growth for OVA: E.G7-OVA, for mWT1: mWT1–1498 cells and for tumor lysate: MHC-I− B16D8 melanoma (T) | [172] |
Tumor-derived plasma membrane vesicles engrafted with two CD11c binding peptides | i.v. | OVA | ↑CD8, ↑humoral, and ↓growth of metastatic B16-OVA (T) | [173] |
| ||||
CD11b
Adenylate cyclase- (CyaA-) based vector |
i.p. vs. i.v. or i.d. | OVA vs. HPV E7 | ↓growth OVA-B16 or E.G7-OVA versus TC-1 (P + T) | [113, 174] |
Phase II study with ProCervix = CyaA-based vector | s.c. | HPV16 and 18 E7 + ADJ | Clinical phase I trial indicated good safety and local tolerance at the highest dose, ↑T + ↑viral clearance + controlled HPV recurrence | NCT01957878 |
| ||||
Fcγ receptor | ||||
| ||||
IgG1-Fc tumor cells | s.c. | TAAs | ↓growth E.G7 (P + T) | [175] |
HER2-Fc cDNA | i.m. + EP | HER2 | Mu: ↑T, ↓growth HER2+ D2F2/E2 cells (P) Hu: in vitro cross-processing and ↑CD8 + T cells from breast cancer patients |
[176] |
| ||||
MHC-II molecule | ||||
| ||||
DNA loaded dendrimer with targeting peptide | s.c. | Trp2 or gp70 vs. OVA | ↑CD8, ↑humoral, ↓growth, strong for B16OVA, and weak for gp70 BUT better with EP (P) ↔ B16 with Trp2 (T) | [177] |
LV pseudotyped with scFv coupled to H protein of measles virus envelope | i.v. | OVA or male HY gene | ↑CD4, ↑cytotoxic, and memory CD8 BUT not to the same extent as broad tropism LVs | [112, 178] |
LV pseudotyped with scFV coupled to murine leukemia virus envelope | s.c. | OVA | ↑CD8 mediated IFNγ secretion | [179] |
DNA encoding anti-MHC II and anti-CD40 scFv or chemokines (MIP-1α, RANTES) with scFV of idiotype | i.m. or i.d. + EP | Idiotypes | ↑CD8, ↑humoral, and ↓growth Id+ tumors (P) | [180, 181] |
| ||||
Non-CLR surface marker | ||||
| ||||
BST2
Protein fused anti-BST2 Ab |
i.p. | OVA or pHEL + ADJ | ↑CD4, ↑CD8, ↑humoral + ↓growth B16-OVA (P) | [182] |
| ||||
Undefined | ||||
| ||||
NP with cholesteryl pullulan towards medullary macrophages | s.c. | MAGE-A4 or mERK2 + ADJ | ↑cross-presentation, ↓growth MAGE-A4+ CMS5+ CT26, and mERK2+ sarcoma cell line (P + T) | [183] |
Listeria monocytogenes expressing TAAs | i.p. | VEGFR2 + ADJ | ↑CD8 with epitope spreading, ↓growth breast tumors (P + T) | [114, 184] |
Coronavirus vector | i.v. | MelanA or Gp33 + ADJ | ↑CD8, expanded epitope repertoire, growth MelanA+ or gp33+ B16F10 (P + T) | [185, 186] |
APC specific nanobody displaying LV | i.n. | OVA | ↑CD4, ↑CD8, ↓growth (T) BUT not to the same extent as broad tropism LVs | [45] |
ISCOM vaccine | s.c. | OVA | ↑CD8, ↓growth EG-7-, B16-, or Panc-OVA (P) | [187] |
| ||||
Costimulatory molecule | ||||
| ||||
CD40
PLGA-NP coated with mAb |
s.c. | OVA and E7 + ADJ | ↑CD8, ↑CD4 + ↓growth B16-OVA (P + T) | [188] |
CD40 targeted adenoviral vector | i.p. | PSMA + ADJ | ↑CD8, ↓growth RM-1-PSMA model (T) | [189] |
CD40L extracellular domain to adenoviral vector in mice + Clinical trial |
i.d. | Mice: Trp2 or gp100 Human: MART-1 |
Mice: ↑CD8, ↓growth B16F10 (T) ↑CD8 in melanoma-draining sentinel lymph nodes |
[190, 191] |
| ||||
B7
Syngeneic epithelial cells continuously secreting CTLA-4-ErbB2 fusion vaccine |
s.c. | HuErbB2 + IL-15 | ↑CD8, ↑humoral, ↓growth ErbB2+ renal cell carcinoma (T) | [192] |
| ||||
Treml4, Ig superfamily member
mAb against Treml4 |
i.p. | OVA or HER2 + ADJ | ↑CD8, ↑CD4, ↓growth neu+ mammary tumor cell line NT2.5 (P) | [193] |
| ||||
TLRs
TLR9 targeting protein (via DNA sequence) |
i.d. | OVA + CpG | TH - independent ↑CD8 + ↓growth E.G7-OVA (P + T) | [194] |
TLR2 targeting lipid moiety + epitopes | s.c. | OVA | ↑CD8, ↑humoral + ↓growth B16-OVA, and Lewis lung-OVA (P + T) | [195] |
TLR5 targeted peptides (via flagellin) engrafted onto liposomes | i.v. | OVA | ↑maturation of DCs, ↑CD8, ↑humoral, ↓growth B16, and P815 (P + T) | [173, 196] |
TLR4 targeting protein (via fibronectin) | i.t. or i.v. | HPV E7 w or w/o ADJ or CPM | ↑CD8 with cure of established TC-1 tumors i.t.: in the absence of additional ADJ i.v.: when + ADJ or CPM + ADJ |
[197] |
TLR4 targeting protein (via fibronectin) + anti-CD40, TLR3 and TLR7 ligands | s.c. | OVA + ADJ | ↑CD8, ↓growth B16-OVA or B16.F10 (T) | [198] |
Chemokine related
Fusion of chemokine MCP3 or IP10 to lymphoma-derived scFv as protein or DNA plasmid |
s.c. or i.d. | scFV | ↑humoral, ↓growth 38C-13 and A20 (P) | [199] |
OVA with mAb or chemokine ligand XCL1 against XCR1 | i.v. | OVA + ADJ | ↑CD8, ↓growth E.G7 (P) | [200] |
P: prophylactic, T: therapeutic, fp: footpad, i.v.: intravenous, s.c.: subcutaneous, i.p.: intraperitoneal, i.m.: intramuscular, EP: electroporated, i.d.: intradermal, i.n.: intranodal, i.t.: intratumoral, U: unknown, ADJ: adjuvant, CPM: cyclophosphamide iNKT: induced natural killer T cell, and in bold: all studies with human APCs.