Cross-species Vascular Endothelial Growth Factor (VEGF)-blocking Antibodies Completely Inhibit the Growth of Human Tumor Xenografts and Measure the Contribution of Stromal VEGF

Liang, Wei-Ching; Wu, Xiumin; Peale, Franklin; Lee, Chingwei V.; Meng, Y. Gloria; Gutierrez, Johnny; Fu, Ling; Malik, Ajay K.; Gerber, Hans‐Peter; Ferrara, Napoleone; Fuh, Germaine

doi:10.1074/jbc.m508199200

Cited by 321 publications

(297 citation statements)

References 38 publications

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“…The anti-VEGF molecule used in this study is known to be a potent antibody to VEGF and has previously been shown to inhibit tumor growth (31), reduce vascular density (7), and reduce the dynamic contrast-enhanced-MRI parameter K trans (33). The second molecule used in this study, anti-NRP1 B , has also been shown to inhibit vascular density (34) and to slow tumor growth when used in combination with anti-VEGF (35).…”

Section: Discussionmentioning

confidence: 99%

“…The first therapy was a highly potent monoclonal anti-VEGF antibody (G6-31) (31), and the second therapy was an antibody to neuropilin-1 (anti-NRP1 B ) (32). The anti-VEGF antibody used in this study blocks both human and murine VEGF-A to ensure that both tumor-and stromaderived VEGF are inhibited.…”

mentioning

confidence: 99%

“…The anti-VEGF antibody used in this study blocks both human and murine VEGF-A to ensure that both tumor-and stromaderived VEGF are inhibited. This anti-VEGF antibody has been shown to suppress tumor growth, vascular density (7,31), dynamic contrast-enhanced ultrasound estimates of blood volume (7), and the perfusion-and permeability-sensitive dynamic contrast-enhanced MRI parameter K trans (33). A humanized anti-VEGF antibody (Avastin V R ; Genentech, Inc.) is currently approved for treatment of multiple human cancers.…”

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confidence: 99%

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Vessel imaging with viable tumor analysis for quantification of tumor angiogenesis

Ungersma

Pacheco²,

et al. 2010

Magnetic Resonance in Med

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Imaging of tumor microvasculature has become an important tool for studying angiogenesis and monitoring antiangiogenic therapies. Ultrasmall paramagnetic iron oxide contrast agents for indirect imaging of vasculature offer a method for quantitative measurements of vascular biomarkers such as vessel size index, blood volume, and vessel density. Here, this technique is validated with direct comparisons to ex vivo micro-CT angiography and histologic vessel measurements, showing significant correlations between in vivo vascular MRI measurements and ex vivo structural vessel measurements. The sensitivity of the MRI vascular parameters is also demonstrated, in combination with a multispectral analysis technique for segmenting tumor tissue to restrict the analysis to viable tumor tissue and exclude regions of necrosis. It is shown that this viable tumor segmentation increases sensitivity for detection of significant effects on blood volume and vessel density by two antiangiogenic therapeutics (anti-VEGF and anti-neuropilin-1) on an HM7 colorectal tumor model. Anti-VEGF reduced blood volume by 36 6 3% (P < 0.0001) and vessel density by 52 6 3% (P < 0.0001) at 48 h posttreatment; the effects of anti-neuropilin-1 were roughly half as strong with a reduction in blood volume of 18 6 6% (P < 0.05) and a reduction in vessel density of 33 6 5% (P < 0.05) at 48 h posttreatment.

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Section: Discussionmentioning

confidence: 99%

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Vessel imaging with viable tumor analysis for quantification of tumor angiogenesis

Ungersma

Pacheco²,

et al. 2010

Magnetic Resonance in Med

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“…Axl is expressed on endothelial cells and enhances vascular endothelial growth factor (VEGF)-induced endothelial tubule formation (Holland et al, 2005;Li et al, 2009); we tested whether anti-Axl mAb could enhance the antitumor growth property of anti-VEGF (Liang et al, 2006). Anti-VEGF antibody alone and YW327.6S2 alone had similar effects on A549 tumor growth (Figure 2a).…”

Section: Generation Of a Phage Derived Mab That Blocks Axl's Functionmentioning

confidence: 99%

An anti-Axl monoclonal antibody attenuates xenograft tumor growth and enhances the effect of multiple anticancer therapies

Stawicki³

et al. 2010

Oncogene

199

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“…The anti-VEGF antibody B20-4.1, which binds both human and murine VEGF with affinity similar to that of bevacizumab (Avastin; Genentech) to human VEGF (35), was therefore tested in the SW527 breast tumor model alone or in combination with h10H5 as above. At weekly doses of 10 mg/kg, B20-4.1 significantly inhibited tumor growth, with TGI of 60% on day 14 (P < 0.0001, relative to vehicle group).…”

Section: Induces Dynamic Changes Of Tumor Transcriptional Profilesmentioning

confidence: 99%

Antixenograft tumor activity of a humanized anti-insulin-like growth factor-I receptor monoclonal antibody is associated with decreased AKT activation and glucose uptake

Shang¹,

Mao²,

Batson³

et al. 2008

Molecular Cancer Therapeutics

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The insulin-like growth factor (IGF) system consists of two ligands (IGF-I and IGF-II), which both signal through IGF-I receptor (IGF-IR) to stimulate proliferation and inhibit apoptosis, with activity contributing to malignant growth of many types of human cancers. We have developed a humanized, affinity-matured anti-human IGF-IR monoclonal antibody (h10H5), which binds with high affinity and specificity to the extracellular domain. h10H5 inhibits IGF-IR-mediated signaling by blocking IGF-I and IGF-II binding and by inducing cell surface receptor downregulation via internalization and degradation, with the extracellular and intracellular domains of IGF-IR being differentially affected by the proteasomal and lysosomal inhibitors. In vitro, h10H5 exhibits antiproliferative effects on cancer cell lines. In vivo, h10H5 shows single-agent antitumor efficacy in human SK-N-AS neuroblastoma and SW527 breast cancer xenograft models and even greater efficacy in combination with the chemotherapeutic agent docetaxel or an anti -vascular endothelial growth factor antibody. Antitumor activity of h10H5 is associated with decreased AKT activation and glucose uptake and a 316-gene transcription profile with significant changes involving DNA metabolic and cell cycle machineries. These data support the clinical testing of h10H5 as a biotherapeutic for IGF-IR-dependent human tumors and furthermore illustrate a new method of monitoring its activity noninvasively in vivo via 2-fluoro-2-deoxy-D-glucose-positron emission tomography imaging. [Mol Cancer Ther 2008;7(9):2599 -608]

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Cross-species Vascular Endothelial Growth Factor (VEGF)-blocking Antibodies Completely Inhibit the Growth of Human Tumor Xenografts and Measure the Contribution of Stromal VEGF

Cited by 321 publications

References 38 publications

Vessel imaging with viable tumor analysis for quantification of tumor angiogenesis

Vessel imaging with viable tumor analysis for quantification of tumor angiogenesis

An anti-Axl monoclonal antibody attenuates xenograft tumor growth and enhances the effect of multiple anticancer therapies

Antixenograft tumor activity of a humanized anti-insulin-like growth factor-I receptor monoclonal antibody is associated with decreased AKT activation and glucose uptake

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