Table 4 Re-targeted TF for cancer therapy

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

α_vβ₃ and α_vβ₅

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)

α_vβ₃ and α_vβ₅

human adenocarcinomas (CCL185), melanoma (M21), and fibrosarcoma (HT1080)

Tumor growth retardation thrombotic occlusion of tumor vessels

[276]

 RGD3-tTF (3 RGD repeat motifs)

α_vβ₃

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

α_vβ₃ and α_vβ₅

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]