Table 4.
Re-targeted TF for cancer therapy
| Agent | Target | Model | Outcome | Ref |
|---|---|---|---|---|
| Antibody-mediated coagulation | ||||
|
Antibody-tTF (B21-2/10HlO-tTF) + IFN-γ |
MHCII (IFN-γ-induced) | C1300(Muγ) mouse neuroblastoma | Thrombosis, complete tumor regression 38% of animals; volume reduction 70% Day 21 | [269] |
| Anti.VCAM-1-tTF | VCAM-1 | L540rec human Hodgkin’s lymphoma | Selective thrombosis; tumor inhibition but complete tumor regressions were not observed | [270] |
|
Antibody-sTF (MK271 and 1G11B1) ± doxorubicin (DOX) |
VCAM-1 | L540rec human Hodgkin’s lymphoma Colo677 human small cell lung cancer (SCLC) ± human vasculature/HDMEC | Short term: tumor necrosis, 74% for L540rec + lipopolysaccharide, 26% for Colo677. Long-term: delayed tumor growth, 30% Colo677 (Day 14), with DOX 90% | [271] |
| chimeric antibody –tTF fusions (chTV-1-tTF) | Fibronectin | MAD109 murine lung carcinoma Colon-26 murine colon | Thrombosis and tumor growth inhibition | [272] |
| scFv-tTF | Fibronectin | F9 murine teratocarcinoma C51 murine colon carcinoma FE8 rat fibroblast sarcoma | High dose, complete tumor regression in 30%, rapid occlusion (1 h) in 50% | [273] |
| chimeric antibody –tTF fusions (chTNT-3-tTF) | Degenerated vasculature (exposed DNA) | MAD109 murine lung carcinoma Colon-26 murine colon | Thrombosis and tumor growth inhibition | [272] |
| scFV-tTF | TEM8 | HT-29 human colorectal carcinoma | Localized thrombosis, 53% reduction in tumor volume | [274] |
| scFv- VIIa (TFOS4) | Fibroblast Activation Protein (FAP) | HT1080 cells | Induced plasma coagulation | [275] |
| Peptide-mediated coagulation | ||||
| RGD-tTF | αvβ3 and αvβ5 | MAD109 murine lung carcinoma Colon-26 murine colon | Thrombosis, no significant inhibition of tumor growth | [272] |
| tTF-RGD (RGD coupled to the COOH-terminal of tTF) | αvβ3 and αvβ5 | human adenocarcinomas (CCL185), melanoma (M21), and fibrosarcoma (HT1080) | Tumor growth retardation thrombotic occlusion of tumor vessels | [276] |
| RGD3-tTF (3 RGD repeat motifs) | αvβ3 | CT26 murine colorectal cancer | Thrombosis and necrosis, tumor growth inhibition, increased survival | [277] |
| tTF–truncated heparin-binding domain (HBD) | Complex (C6S, VEGFR2, NRP-1) | N202 murine mammary carcinoma | Rapid thrombosis, significant tumor eradication; FVIIa co-administration | [278] |
| SP5.2/tTF-OCMCs-SPIO-NPs | VEGFR-1 | SMMC-7721 human hepatocarcinoma | Conjugated embolic nanoparticle thrombosis and vessel occlusion were observed > SP5.2-tTF alone | [279] |
| SP5.2-tTF | VEGFR-1 | S180 murine sarcoma | Thrombosis, growth inhibition/regression 70% Day 6 | [280] |
| tTF-EG3287 | Neuropilin-1 | HepG2 human liver cancer | Thrombosis and necrosis, tumor growth reduction | [281] |
| tTF-EG3287 | Neuropilin-1 | HT29 human colon adenocarcinoma | Thrombosis | [282] |
| tTF-EG3287 iron oxide NPs | Neuropilin-1 | HepG2 human liver cancer | Thrombosis, necrosis, tumor growth inhibition | [283] |
|
tTF-TAA tTF-NGR |
NG2 | A549 human lung adenocarcinoma M21 human melanoma | Lower anti-tumor activity and smaller therapeutic window of tTF-NGR relative to tTF-NGR | [284] |
| tTF-NGR | Aminopeptidase N (CD13) | A549 human lung adenocarcinoma M21 human melanoma HT1080 human fibrosarcoma + Low dosage clinical study (First-in-man, 5 terminal cancer patients | Animal studies: Vascular tumor volume reduction, regression at high s.c. but some toxicity | [285] |
| tTF-CREKA | Fibrin-fibronectin complexes | LS174T human liver cancer 4T1 human breast cancer MHCC97H human liver cance | Thrombosis, tumor growth inhibition | [286] |
| PSMA catalytic site inhibitor-tTF + Doxil | PSMA (prostate-specific marker antigen) | Rat Mat Lu prostate tumor LuCap human prostate tumor | Microvessel infarction, tumor growth inhibition | [287] |
| Antibody -streptavidin + tTF-biotin | Neuropilin-1 | HepG2 human liver cancer | Thrombosis, tumor growth reduction and necrosis | [288] |
| CREKA-SPIO nanoparticles | Fibrin-fibronectin complexes | MDA-MB-435 human breast cancer | Low tumor growth inhibition | [289] |
| tTF-pHLIP | Acidic tumor matrix | MDA-MB-231 human breast cancer | Thrombosis, rapid tumor regression | [264] |
| tTF-pHLIP | Acidic tumor matrix | B16-F10 murine melanoma | Tumor growth inhibition | [290] |
| Non-coagulant application | ||||
|
RGD-Doxorubicin NGR-Doxorubicin |
αvβ3 and αvβ5 NG2 aminopeptidase N (CD13) |
MDA-MB-435 human breast cancer | Effective antitumor activity, prolongation of survival | [291] |
| CREKA-Lipo-T | Fibrin-fibronectin complexes | 4T1 mouse breast cancer | Inhibited tumor metastasis | [292] |
| TV.1-IL-2 | basement membrane antigen |
LS 174 T human colorectal cancer ME-180 human cervical carcinoma |
Enhance uptake of monoclonal antibodies | [293] |
| CREKA-Tris (Gd-DOTA)3 | Fibrin-fibronectin complexes | 4T1 mouse breast cancer | Effectively visualize metastases containing micro-metastases | [294] |