Table 3.

Targeting  TF for cancer therapy

Agent	Target	Model	Outcome	Ref
Monoclonal antibody
Anti-β1 integrin antibody (HUTS-21)	β-tail domain (βTD) of the β1 integrin subunit	Breast cancer models in vitro and in vivo	Reduction of the asTF-dependent proliferation of tumor cells	[60]
Anti-asTF antibody (Rabmab1)	asTF	PDAC cell line (Pt45.P1) in vivo	progression and spread restriction	[59]
Anti-TF antibody SC1	TF extracellular domain, PAR2 signaling	Broad triple-negative breast cancer cell lines and Pancreatic adenocarcinoma cancer cell lines in vitro and in vivo	inhibition of TF-induced cell migration, lung metastasis, and tumor growth. Diminished levels of tumor angiogenesis and stromal fibrosis of triple-negative breast cancer and Pancreatic adenocarcinoma cancer	[190]
10H10	TF (signaling)	Murine model In vivo	Delayed progression of GBM cells harboring EGFRvIII	[193]
CNTO 859	TF (coagulation)	Murine model In vivo	Delayed progression of GBM cells harboring EGFRvIII	[193]
Antibody drug conjugate
SC1-DM	TF	Broad TNBC and PaC cell lines in vitro and in vivo	Cytotoxic effects in TF-positive TNBC and PaC cancers	[190]
SC1-MMAE	TF	Broad TNBC and PaC cell lines in vitro and in vivo	Cytotoxic effects in TF-positive TNBC and PaC cancers	[190]
Tisotumab vedotin (InnovaTV 201)	TF	Broad cancers, clinical trial	Anti-cancer activity	[194–197]
Anti-human TF (clone 1849)-MMAE	TF	several pancreatic cancer cell lines, in vitro and in vivo	Suppression of tumor growth	[198]
Anti-TF1859-NC-6300 (epirubicin-incorporating micell)	TF	BxPC3 and SUIT2 pancreatic cancer, in vitro and in vivo	Anti-cancer activity	[199]
Anti-TF-NC-6300	TF	BxPC3, SUIT2 and 44AS3 pancreatic and gastric cancer in vitro and in vivo	Anti-cancer activity	[200]
TF-011-MMAE	TF interruption of TF: FVIIa-dependent intracellular signaling	patient-derived xenograft (PDX) originating from seven diverse solid cancers in vitro and in vivo	Anti-cancer activity	[189]
mfVII/human Fc icon	TF/chondroitin sulfate	Several cancer models	Activation of the complement system and NK cell inhibition of growth and relapse of an established human tumor model	[201–206]
PAR1 pepducins	first (i1) and third (i3) intracellular PAR1 loops	lung cancer cell lines in vivo	meaningful cell migration hindrance	[207]
PAR1 pepducin	third (i3) intracellular PAR1 loop	lung cancer cell lines in vivo	Inhibition of cancer cell proliferation	[207]
imidazopyridazine compound I-191	PAR2	MDA-MB-231 human breast adenocarcinoma cell line and HT29 human colon adenocarcinoma cell line	Inhibition of PAR2 intracellular signal pathways	[208]
TF ligand inhibitor
Rivaroxaban	coagulation factor X (FX) and PAR2 signal transduction	Peripheral blood monocytes and neutrophils and murine model In vitro, in vivo pancreatic tumor models In vivo	increasing infiltration of dendritic cells and cytotoxic T cells at the tumor region, but could not reduce growth of pancreatic tumor models	[209, 210]
PCI-27483	TF: FVIIa-complex and PAR2 signaling	BXPC3 pancreatic tumor mice model	significant dose-dependent tumor growth	[211]
rNAPc2
rNAPc2	TF/FVIIa complex inhibition	B16F10 melanoma cell line In vivo	primary and metastatic tumor growth and angiogenesis	[212]
CAR cell
TF-CAR T cell	TF	non-small cell lung cancer (NSCLC) cells and melanoma cells in vitro and in xenograft and metastasis models of human NSCLC in NOG mice	In vitro: strong cytotoxic potential In vivo: significant suppression of s.c. xenograft growth and lung metastasis models	[213]
TF-CAR NK cell (single and combination therapy with L-ICON)	TF	TNBC cell lines in vitro TNBC cell lines and patient’s tumor-derived xenograft mouse models in vivo	in vitro: TF-CAR-NK cells alone could kill TNBC cells, and its efficacy was enhanced with L-ICON ADCC in vivo: effective treatment of TNBC cell line- and patient’s tumor-derived xenograft mouse models	[27]
Vitamin K antagonist
Warfarin	Gas6-dependent Axl activation	Pancreatic cancer cell lines in vitro and in vivo	Inhibition of development, spread, migration, invasiveness, and proliferation of pancreatic cancer cells	[214]
Antibody-mediated imaging
Anti- TF antibody (ALT-836)	factor X/factor IX (FX/FIX) binding site of TF	surgical endarterectomy model in chimpanzees In vivo	Prevention of thrombin generation and acute vascular thrombosis	[215]
64Cu-NOTA-ALT-836	factor X/factor IX (FX/FIX) binding site of TF	Pancreatic cancer cell lines in vitro, in vivo and ex vivo Thyroid cancer cell lines In vivo	More uptake in BXPC-3 tumors (high TF expression) than in PANC-1 and ASPC-1 tumors (lower TF expression Suppression of subcutaneous and orthotopic anaplastic thyroid cancer (ATC) with high levels of tumor uptake	[216, 217]
(64)Cu-NOTA-ALT-836-Fab	factor X/factor IX (FX/FIX) binding site of TF	MDA-MB-231 TNBC model	Several-fold greater tumor uptake compared to the blocking group and tumor models that failed to significantly express TF	[218]
89Zr-Df-ALT-836	factor X/factor IX (FX/FIX) binding site of TF	Pancreatic cancer cell lines in vitro, in vivo, ex vivo	long-term and prominent uptake in BXPC-3 tumors	[219]
Heterodimer of TRC-105 and ALT-836 dual radiolabeled with 64Cu heterodimer-ZW800	TRC-105: CD105 ALT-836: factor X/factor IX (FX/FIX) binding site of TF	Mice models of pancreatic cancer	High tumor uptake	[220]
64Cu-NOTA-ALT-836 IRDye 800CW-ALT-836 (near-infrared fluorescent imaging probe) 131I-ALT-836 (radioimmunotherapy)	factor X/factor IX (FX/FIX) binding site of TF	Anaplastic thyroid cancer (ATC) in vivo and ex vivo	a peak tumor uptake leads to both subcutaneous and orthotopic suppression of ATC prolongs the survival of ATC-bearing mice	[217]
18F-FVIIai	TF	mouse model of human pancreatic cancer In vivo and ex vivo	significant uptake of 18F-FVIIai by TF-expressed tumors	[221]