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 | |
 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 | |
 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 | |
 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 | |
 (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] |