Utility of epirubicin‐incorporating micelles tagged with anti‐tissue factor antibody clone with no anticoagulant effect

Sugaya, Akinori; Hyodo, Ichinosuke; Koga, Yoshikatsu; Yamamoto, Yoshiyuki; Takashima, Hiroki; Sato, Ryuta; Tsumura, Ryo; Furuya, Fumiaki; Yasunaga, Masahiro; Harada, Mitsunori; Tanaka, Ryosuke; Matsumura, Yasuhiro

doi:10.1111/cas.12863

Cited by 18 publications

(13 citation statements)

References 16 publications

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“…This anti-TF antibody-conjugate reduced the growth of BxPc-3 subcutaneous tumors but not SUIT2 subcutaneous tumors. 103 Three groups developed different anti-TF antibody conjugates with monomethyl auristatin E (MMAE). [104][105][106] MMAE inhibits cell division of actively dividing cells by blocking the polymerization of tubulin and shows an antitumor effect.…”

Section: Targeting Tissue Factor As a Novel Anticancer Therapymentioning

confidence: 99%

Tissue Factor and Cancer: Regulation, Tumor Growth, and Metastasis

Hisada

Mackman

2019

Semin Thromb Hemost

120

108

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There is a strong relationship between tissue factor (TF) and cancer. Many cancer cells express high levels of both full-length TF and alternatively spliced (as) TF. TF expression in cancer is associated with poor prognosis. In this review, the authors summarize the regulation of TF expression in cancer cells and the roles of TF and asTF in tumor growth and metastasis. A variety of different signaling pathways, transcription factors and micro ribonucleic acids regulate TF gene expression in cancer cells. The TF/factor VIIa complex enhances tumor growth by activating protease-activated receptor 2 signaling and by increasing the expression of angiogenic factors, such as vascular endothelial growth factor. AsTF increases tumor growth by enhancing integrin β1 signaling. TF and asTF also contribute to metastasis via multiple thrombin-dependent and independent mechanisms that include protecting tumor cells from natural killer cells. Finally, a novel anticancer therapy is using tumor TF as a target to deliver cytotoxic drugs to the tumor. TF may be useful in diagnosis, prognosis, and treatment of cancer.

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Section: Targeting Tissue Factor As a Novel Anticancer Therapymentioning

confidence: 99%

Tissue Factor and Cancer: Regulation, Tumor Growth, and Metastasis

Hisada

Mackman

2019

Semin Thromb Hemost

120

108

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“…Previous reports have suggested that cytokine‐induced and/or chemokine‐induced TF expression in tumor cells and tumor‐connective tissues promotes neo‐angiogenesis, invasion, and metastasis in ovarian cancer . Recently, Matsumura's group . demonstrated that the systemic administration of selective anti‐TF antibody conjugated with an anti‐cancer drug was effective for growth inhibition of human pancreatic and gastric cancer cell lines using murine intravenous xenograft models without affecting coagulant activity.…”

Section: Discussionmentioning

confidence: 99%

Novel strategy of ovarian cancer implantation: Pre‐invasive growth of fibrin‐anchored cells with neovascularization

et al. 2019

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Although direct adhesion of cancer cells to the mesothelial cell layer is considered to be a key step for peritoneal invasion of ovarian cancer cell masses (OCM), we recently identified a different strategy for the peritoneal invasion of OCM. In 6 out of 20 cases of ovarian carcinoma, extraperitoneal growth of the OCM was observed along with the neovascularization of feeding vessels, which connect the intraperitoneal host stroma and extraperitoneal lesions through the intact mesothelial cell layer. As an early step, the OCMs anchor in the extraperitoneal fibrin networks and then induce the migration of CD34‐positive and vascular endothelial growth factor A (VEGF‐A)‐positive endothelial cells, constructing extraperitoneal vascular networks around the OCM. During the extraperitoneal growth of OCM, podoplanin‐positive and α smooth muscle actin (αSMA)‐positive cancer‐associated fibroblasts (CAF) appears. In more advanced lesions, the boundary line of mesothelial cells disappears around the insertion areas of feeding vessels and then extraperitoneal and intraperitoneal stroma are integrated, enabling the OCM to invade the host stroma, being associated with CAF. In addition, tissue factors (TF) are strongly detected around these peritoneal implantation sites and their levels in ascites were higher than that in blood. These findings demonstrate the presence of neovascularization around fibrin net‐anchored OCMs on the outer side of the intact peritoneal surface, suggesting a novel strategy for peritoneal invasion of ovarian cancer and TF‐targeted intraperitoneal anti‐cancer treatment. We observed and propose a novel strategy for peritoneal implantation of ovarian cancer. The strategy includes the preinvasive growth of fibrin‐anchored cancer cells along with neovascularization on the outer side of the intact peritoneal surface.

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“…Non-specific binding was blocked by applying Block Ace reagent (Dainippon Pharmaceutical Co., Ltd., Osaka, Japan) with 10% goat serum for 30 min at room temperature. Cells were incubated with anti-TF antibody 1849 (rat IgG 2b ) (26,30) as a primary antibody overnight at 4˚C. A secondary anti-rat antibody conjugated with Cy3 (diluted 1:1,000; cat.…”

Section: Methodsmentioning

confidence: 99%

Anti‑tissue factor antibody‑mediated immuno‑SPECT imaging of tissue factor expression in mouse models of pancreatic cancer

et al. 2019

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Tissue factor (TF) has emerged as a critical factor in oncogenic events, leading to the development of TF-targeted diagnostic and therapeutic approaches. A non-invasive imaging method to evaluate target molecule expression with high sensitivity and high quantitative ability is imperative for selecting the appropriate patients for TF-targeted therapy. To elucidate the potential of 111 In-labeled anti-TF antibody 1849 ( 111 In-1849) as an immuno-single photon emission computed tomography (SPECT) probe targeting TF, we evaluated TF-dependent in vitro binding as well as in vivo biodistribution and tumor accumulation of 111 In-1849 in pancreatic cancer cells/models with varying TF expression levels. TF expression levels in five human pancreatic cancer cell lines, BxPC-3, BxPC-3-TF-knockout (BxPC-3-TFKO), Capan-1, PSN-1 and SUIT-2, were examined by immunofluorescence. Binding of 111 In-1849 to each cell line was assessed. Biodistribution and imaging studies were also conducted in tumor-bearing mice.Furthermore, the relationship of TF expression with cell binding and tumor uptake was analyzed. In the immunofluorescence studies, BxPC-3 exhibited the highest TF expression, followed by Capan-1, PSN-1, SUIT-2 and BxPC-3-TFKO. Cell binding assays revealed that BxPC-3 cells had the highest 111 In-1849 binding, followed by PSN-1, Capan-1 and SUIT-2; no binding was detected in BxPC-3-TFKO cells. The BxPC-3 xenograft was clearly visualized on 111 In-1849 SPECT/CT, and the highest uptake was detected on day 4. The biodistribution of 111 In-1849 on day 4 revealed that tumor uptake ranged from 8.68 to 50.58% of the injected dose per gram of tissue; BxPC-3 had the highest uptake and SUIT-2 had the lowest. TF expression was significantly associated with cell binding (R 2 =0.79, P<0.05) and tumor uptake (R 2 =0.92, P<0.01). The association of 111 In-1849 uptake with TF expression suggests the potential application of non-invasive imaging with radiolabelled 1849 for selecting the appropriate patients who would likely respond to TF-targeted therapies in clinical practice.

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Utility of epirubicin‐incorporating micelles tagged with anti‐tissue factor antibody clone with no anticoagulant effect

Cited by 18 publications

References 16 publications

Tissue Factor and Cancer: Regulation, Tumor Growth, and Metastasis

Tissue Factor and Cancer: Regulation, Tumor Growth, and Metastasis

Novel strategy of ovarian cancer implantation: Pre‐invasive growth of fibrin‐anchored cells with neovascularization

Anti‑tissue factor antibody‑mediated immuno‑SPECT imaging of tissue factor expression in mouse models of pancreatic cancer

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