A Humanized Anti-VEGF Rabbit Monoclonal Antibody Inhibits Angiogenesis and Blocks Tumor Growth in Xenograft Models

Yu, Yang; Leblond, Pierre; Ke, Yaohuang; Zhang, Yongke; Qiu, Yu; Jonathan, L Finlay; Li, Mingzhen; Jialiang, Song; Chen, Jungang; Dai, Jihong; Couto, Fernando Jose Rebelo Do; An, Zhiqiang; Zhu, Weimin; Yu, Guo Liang

doi:10.1371/journal.pone.0009072

Cited by 56 publications

(51 citation statements)

References 53 publications

(67 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[29][30][31][32] It has also been demonstrated that TSP1 can mediate tumor growth suppression via blocking angiogenesis, consistent with our results. 33,34 As previously mentioned HuR has been described to stabilize TSP1 and VEGF mRNA resulting in greater levels and increased protein expression.…”

Section: Discussionsupporting

confidence: 92%

Overexpression of the RNA binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis

et al. 2010

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 92%

Overexpression of the RNA binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis

et al. 2010

View full text Add to dashboard Cite

“…To study the impact of VEGF-specific blockades on vasculatures in various healthy tissues, we used three specific anti-VEGF agents known to block VEGF-induced biological activities: a rabbit anti-mouse neutralizing monoclonal antibody (BD0801) (22); a rat anti-mouse VEGFR-1 neutralizing monoclonal antibody (MF-1) (23)(24)(25); and a rat anti-mouse VEGFR-2 neutralizing monoclonal antibody (DC101) (23)(24)(25). These antibodies were systemically delivered for 2 wk to healthy mice using doses known to block tumor angiogenesis (22)(23)(24)(25).…”

Section: Resultsmentioning

confidence: 99%

“…These antibodies were systemically delivered for 2 wk to healthy mice using doses known to block tumor angiogenesis (22)(23)(24)(25). Because bevacizumab (a humanized anti-human VEGF neutralizing monoclonal antibody) is widely being used for treatment of various human cancers (2,(17)(18)(19)(20)(21) and ramucirumab (a humanized antihuman VEGFR-2 neutralizing monoclonal antibody) together with docetaxel-based chemotherapy is planned for a phase III trial for treatment of non-small cell lung carcinoma (26), systemic treatment with the same agents designed in our study would be clinically relevant.…”

Section: Resultsmentioning

confidence: 99%

Anti-VEGF– and anti-VEGF receptor–induced vascular alteration in mouse healthy tissues

Yang

Zhang

Cao

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

121

122

View full text Add to dashboard Cite

Systemic therapy with anti-VEGF drugs such as bevacizumab is widely used for treatment of human patients with various solid tumors. However, systemic impacts of such drugs in host healthy vasculatures remain poorly understood. Here, we show that, in mice, systemic delivery of an anti-VEGF or an anti–VEGF receptor (VEGFR)-2 neutralizing antibody caused global vascular regression. Among all examined tissues, vasculatures in endocrine glands, intestinal villi, and uterus are the most affected in response to VEGF or VEGFR-2 blockades. Thyroid vascular fenestrations were virtually completely blocked by VEGF blockade, leading to marked accumulation of intraendothelial caveolae vesicles. VEGF blockade markedly increased thyroid endothelial cell apoptosis, and withdrawal of anti-VEGF resulted in full recovery of vascular density and architecture after 14 d. Prolonged anti-VEGF treatment resulted in a significant decrease of the circulating level of the predominant thyroid hormone free thyroxine, but not the minimal isoform of triiodothyronine, suggesting that chronic anti-VEGF treatment impairs thyroid functions. Conversely, VEGFR-1–specific blockade produced virtually no obvious phenotypes. These findings provide structural and functional bases of anti-VEGF–specific drug-induced side effects in relation to vascular changes in healthy tissues. Understanding anti-VEGF drug-induced vascular alterations in healthy tissues is crucial to minimize and even to avoid adverse effects produced by currently used anti-VEGF–specific drugs.

show abstract

“…Our findings demonstrate that vasculatures in endocrine organs are more perceptive than those in tumors in response to antiangiogenic treatment. To study the impact of anti-VEGF drug therapy on tumor and healthy vasculatures, we used a rabbit anti-mouse VEGF neutralizing antibody (VEGF blockade) that has been shown to effectively inhibit tumor angiogenesis (10,21,27,28). In two different mouse tumor models, including T241 fibrosarcoma and Lewis lung carcinoma (LLC), titration of different dosages of VEGF blockade showed dose-dependent inhibition of tumor growth.…”

Section: Significancementioning

confidence: 99%

Endocrine vasculatures are preferable targets of an antitumor ineffective low dose of anti-VEGF therapy

Zhang

Yang

Hosaka

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Anti-VEGF–based antiangiogenic drugs are designed to block tumor angiogenesis for treatment of cancer patients. However, anti-VEGF drugs produce off-tumor target effects on multiple tissues and organs and cause broad adverse effects. Here, we show that vasculatures in endocrine organs were more sensitive to anti-VEGF treatment than tumor vasculatures. In thyroid, adrenal glands, and pancreatic islets, systemic treatment with low doses of an anti-VEGF neutralizing antibody caused marked vascular regression, whereas tumor vessels remained unaffected. Additionally, a low dose of VEGF blockade significantly inhibited the formation of thyroid vascular fenestrae, leaving tumor vascular structures unchanged. Along with vascular structural changes, the low dose of VEGF blockade inhibited vascular perfusion and permeability in thyroid, but not in tumors. Prolonged treatment with the low-dose VEGF blockade caused hypertension and significantly decreased circulating levels of thyroid hormone free-T3 and -T4, leading to functional impairment of thyroid. These findings show that the fenestrated microvasculatures in endocrine organs are more sensitive than tumor vasculatures in response to systemic anti-VEGF drugs. Thus, our data support the notion that clinically nonbeneficial treatments with anti-VEGF drugs could potentially cause adverse effects.

show abstract

A Humanized Anti-VEGF Rabbit Monoclonal Antibody Inhibits Angiogenesis and Blocks Tumor Growth in Xenograft Models

Cited by 56 publications

References 53 publications

Overexpression of the RNA binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis

Overexpression of the RNA binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis

Anti-VEGF– and anti-VEGF receptor–induced vascular alteration in mouse healthy tissues

Endocrine vasculatures are preferable targets of an antitumor ineffective low dose of anti-VEGF therapy

Contact Info

Product

Resources

About