Dendritic cells transduced with TEM8 recombinant adenovirus prevents hepatocellular carcinoma angiogenesis and inhibits cells growth

Xiong, Yijun; Zhu, Hai‐Lei; Zhangxue, Hu

doi:10.1016/j.vaccine.2010.07.014

Cited by 15 publications

(14 citation statements)

References 32 publications

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“…However, murine B16 melanoma tumor growth was impaired in Tem8 KO versus wildtype (WT) mice demonstrating that host-derived TEM8 can promote tumor growth on an immunocompetent background (Cullen et al, 2009). Furthermore, previous studies have shown that a soluble TEM8-Fc trap, TEM8 vaccines or sublethal doses of anthrax toxin can inhibit angiogenesis, slow tumor growth, and prolong survival (Duan et al, 2007; Felicetti et al, 2007; Liu et al, 2008; Rouleau et al, 2008; Ruan et al, 2009; Yang et al, 2010). Taken together, these studies suggest that TEM8 may be required for tumor angiogenesis, but not physiological angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

TEM8/ANTXR1 Blockade Inhibits Pathological Angiogenesis and Potentiates Tumoricidal Responses against Multiple Cancer Types

et al. 2012

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SUMMARY Current anti-angiogenic agents used to treat cancer only partially inhibit neovascularization and cause normal tissue toxicities, fueling the need to identify therapeutic agents that are more selective for pathological angiogenesis. Tumor Endothelial Marker 8 (TEM8), also known as anthrax toxin receptor 1 (ANTXR1), is a highly conserved cell-surface protein overexpressed on tumor-infiltrating vasculature. Here, we show that genetic disruption of Tem8 results in impaired growth of human tumor xenografts of diverse origin including melanoma, breast, colon, and lung cancer. Furthermore, antibodies developed against the TEM8 extracellular domain blocked anthrax intoxication, inhibited tumor-induced angiogenesis, displayed broad anti-tumor activity and augmented the activity of clinically approved anti-cancer agents without added toxicity. Thus, TEM8 targeting may allow selective inhibition of pathological angiogenesis.

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Section: Introductionmentioning

confidence: 99%

TEM8/ANTXR1 Blockade Inhibits Pathological Angiogenesis and Potentiates Tumoricidal Responses against Multiple Cancer Types

et al. 2012

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“…Vaccine therapy using targeted molecules, such as tumor endothelial marker 1, TEM8, fibroblast growth factor receptor or VEGFR2, which are overexpressed on TECs, has been studied by many investigators. [31][32][33][34] However, a TEC-specific vaccine therapy with few side-effects has not been developed as yet since such molecules are also expressed on the cell surface of normal blood vessel endothelial cells. In this regard, our results strongly suggest that tumor vaccine therapy only targets tumor, but not physiological, angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Cancer Vaccine Therapy Using Tumor Endothelial Cells as Antigens Suppresses Solid Tumor Growth and Metastasis

Nomura

Hirata

Shimaoka

et al. 2017

Biological & Pharmaceutical Bulletin

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Tumor angiogenesis plays an important role in tumor growth and metastasis, with tumor cells requiring nutrients and oxygen via blood flow for their proliferation. In comparison, angiogenesis also occurs under normal physiological conditions, such as wound healing and in the formation of the corpus luteum. Herein, we report on the development of a novel dendritic cell (DC) vaccine therapy using tumor endothelial cells (TECs) derived from tumor vessels as tumor antigens. After density gradient centrifugation and the detection of angiotensin-converting enzyme activities, a TEC-rich fraction was separated from solid tumor tissues. Prophylactic or therapeutic immunization using DCs pulsed with TECs as vaccine antigens significantly suppressed solid tumor growth in a Colon-26 colorectal adenocarcinoma tumor-bearing mouse model, compared with the use of tumor cells as DC vaccine antigens. Tumor tissues showed reduced angiogenesis. However, vaccination using DCs pulsed with TECs did not inhibit physiological angiogenesis as evidenced by a wound healing assay. Additionally, in a B16/BL6 mouse melanoma lung metastasis model, DC vaccination using TECs derived not only from the same tumor tissue but from a different type of tumor also suppressed metastasis. These results thus show that cancer vaccine therapy targeting TECs is an effective therapy against angiogenesis in several types of cancer, but does not affect normal blood vessel growth.Key words tumor endothelial cell; angiogenesis; dendritic cell; vaccine; metastasis Endothelial cells that enable tumor angiogenesis are recruited from neighboring, pre-existing capillaries 1,2) by tumor angiogenesis mediators, such as vascular endothelial growth factor (VEGF),3) fibroblast growth factors, 4) and transforming growth factor, 5) in the process of tumor progression or metastasis.6,7) Newly produced blood vessels, which are constructed by tumor endothelial cells (TECs), provide oxygen and nutrients, and remove metabolic waste from tumor cells; tumor cell proliferation also depends on new blood vessel formation. 6,8) In addition, TECs in different types of cancers express common, tumor-associated antigens (TAAs), since the tumor's new blood vessels are constructed from endothelial cells of the host. In this regard, it is expected that the inhibition of angiogenesis in tumor tissue will effectively induce tumor regression for several types of cancer, compared with the direct inhibition of tumor cells themselves. In fact, several antiangiogenic agents, such as the VEGF receptor and tyrosine kinase inhibitor, sunitinib, 9) and the anti-VEGF antibody, bevacizumab, 10) are commonly applied in clinical practice today since they tend to show a survival advantage for patients. However, angiogenesis also occurs during the processes of wound healing and corpus luteum formation, 11) with the implication that the clinical application of antiangiogenic agents in cancer patients may result in damage to normal blood vessels, 12) in addition to those of the tumor. Therefore, the selective in...

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“…Ruan et al developed a xenogeneic TEM8 DNA vaccine carried by xenogeneic Salmonella typhimurium that was capable of generating TEM8-specific CD8+ cytotoxic T cells and protected mice from lethal tumor challenge [ 97 ]. Another vaccination approach consisted of dendritic cells transduced with recombinant adenovirus encoding TEM8, which also effectively protected mice from lethal challenges against hepatocellular carcinoma [ 98 ]. Lastly, a DNA vaccine encoding syngeneic TEM8 and murine beta-defensin 2, which activates dendritic cells to stimulate potent immunity, was used to inhibit tumor growth in a murine colon cancer model [ 99 ].…”

Section: Vaccines Targeting Defined Angiogenesis-associated Antigensmentioning

confidence: 99%

Cancer anti-angiogenesis vaccines: Is the tumor vasculature antigenically unique?

Wagner

Ichim

et al. 2015

J Transl Med

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Angiogenesis is essential for the growth and metastasis of solid tumors. The tumor endothelium exists in a state of chronic activation and proliferation, fueled by the tumor milieu where angiogenic mediators are aberrantly over-expressed. Uncontrolled tumor growth, immune evasion, and therapeutic resistance are all driven by the dysregulated and constitutive angiogenesis occurring in the vasculature. Accordingly, great efforts have been dedicated toward identifying molecular signatures of this pathological angiogenesis in order to devise selective tumor endothelium targeting therapies while minimizing potential autoimmunity against physiologically normal endothelium. Vaccination with angiogenic antigens to generate cellular and/or humoral immunity against the tumor endothelium has proven to be a promising strategy for inhibiting or normalizing tumor angiogenesis and reducing cancer growth. Here we review tumor endothelium vaccines developed to date including active immunization strategies using specific tumor endothelium-associated antigens and whole endothelial cell-based vaccines designed to elicit immune responses against diverse target antigens. Among the novel therapeutic options, we describe a placenta-derived endothelial cell vaccine, ValloVax™, a polyvalent vaccine that is antigenically similar to proliferating tumor endothelium and is supported by pre-clinical studies to be safe and efficacious against several tumor types.

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Dendritic cells transduced with TEM8 recombinant adenovirus prevents hepatocellular carcinoma angiogenesis and inhibits cells growth

Cited by 15 publications

References 32 publications

TEM8/ANTXR1 Blockade Inhibits Pathological Angiogenesis and Potentiates Tumoricidal Responses against Multiple Cancer Types

TEM8/ANTXR1 Blockade Inhibits Pathological Angiogenesis and Potentiates Tumoricidal Responses against Multiple Cancer Types

Cancer Vaccine Therapy Using Tumor Endothelial Cells as Antigens Suppresses Solid Tumor Growth and Metastasis

Cancer anti-angiogenesis vaccines: Is the tumor vasculature antigenically unique?

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