Anti-VEGFR2 and anti-IGF-1R-Adnectins inhibit Ewing’s sarcoma A673-xenograft growth and normalize tumor vascular architecture

Ackermann, Maximilian; Morse, Brent; Delventhal, Vera; Carvajal, Irvith M.; Konerding, Moritz A.

doi:10.1007/s10456-012-9294-9

Cited by 58 publications

(45 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The latter is a well-characterized morphogenetic process which can be observed during growth and remodeling of pre-existing networks [8, 9]. A distinguishing anatomic feature of intussusceptive angiogenesis is the intussusceptive pillar.…”

Section: Introductionmentioning

confidence: 99%

Sprouting and intussusceptive angiogenesis in postpneumonectomy lung growth: mechanisms of alveolar neovascularization

et al. 2013

Self Cite

View full text Add to dashboard Cite

In most rodents and some other mammals, the removal of one lung results in compensatory growth associated with dramatic angiogenesis and complete restoration of lung capacity. One pivotal mechanism in neoalveolarization is neovascularization, because without angiogenesis new alveoli can not be formed. The aim of this study is to image and analyze three-dimensionally the different patterns of neovascularization seen following pneumonectomy in mice on a sub-micron-scale. C57/BL6 mice underwent a left-sided pneumonectomy. Lungs were harvested at various timepoints after pneumonectomy. Volume analysis by microCT revealed a striking increase of 143 percent in the cardiac lobe 14 days after pneumonectomy. Analysis of microvascular corrosion casting demonstrated spatially heterogenous vascular densitities which were in line with the perivascular and subpleural compensatory growth pattern observed in anti-PCNA-stained lung sections. Within these regions an expansion of the vascular plexus with increased pillar formations and sprouting angiogenesis, originating both from pre-existing bronchial and pulmonary vessels was observed. Also, type II pneumocytes and alveolar macrophages were seen to participate actively in alveolar neo-angiogenesis after pneumonectomy. 3D-visualizations obtained by high-resolution synchrotron radiation X-ray tomographic microscopy showed the appearance of double-layered vessels and bud-like alveolar baskets as have already been described in normal lung development. Scanning electron microscopy data of microvascular architecture also revealed a replication of perialveolar vessel networks through septum formation as already seen in developmental alveolarization. In addition, the appearance of pillar formations and duplications on alveolar entrance ring vessels in mature alveoli are indicative of vascular remodeling. These findings indicate that sprouting and intussusceptive angiogenesis are pivotal mechanisms in adult lung alveolarization after pneumonectomy. Various forms of developmental neoalveolarization may also be considered to contribute in compensatory lung regeneration.Electronic supplementary materialThe online version of this article (doi:10.1007/s10456-013-9399-9) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

Sprouting and intussusceptive angiogenesis in postpneumonectomy lung growth: mechanisms of alveolar neovascularization

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…Adnectins are extracellular type III domain of human fibronectin derived scaffold proteins with a molecular weight of about 10 kDa [15]. The domain has a structure similar to antibody variable domains.…”

Section: Monobodies/adnectinmentioning

confidence: 99%

Biologicals and Biosimilars

Ghose¹,

Grütter²

2014

New Chemistry and New Opportunities From the Expanding Protein Universe

View full text Add to dashboard Cite

“…Treatment with AT580Peg40 inhibits IGF-mediated VEGF secretion. The combination inhibition of IGF and VEGF signaling with CT-322 and AT580Peg40 significantly inhibits primary tumor growth and angiogenesis [9].…”

Section: Pre-clinical Studiesmentioning

confidence: 99%

Adnectin-Targeted Inhibitors: Rationale and Results

et al. 2015

View full text Add to dashboard Cite

Adnectins are a family of binding proteins derived from the 10th type III domain of human fibronectin (10Fn3), which is part of the immunoglobulin superfamily and normally binds integrin. The 10Fn3 has the potential for broad therapeutic applications given its structural stability, ability to be manipulated, and its abundance in the human body. The most commonly studied adnectin is CT-322, which is an inhibitor of vascular endothelial growth factor receptor-2. A bispecific adnectin, El-Tandem, has also been developed and binds to epidermal growth factor receptor and insulin-like growth factor-1 receptor simultaneously. Pre-clinical studies have shown promising results in relation to reducing tumor growth, decreasing microvessel density, and promoting normalization of tumor architecture. The phase I trial with CT-322 demonstrates relatively low toxicities. However, the phase II study done with CT-322 in recurrent glioblastoma does not reveal as promising results.

show abstract

Anti-VEGFR2 and anti-IGF-1R-Adnectins inhibit Ewing’s sarcoma A673-xenograft growth and normalize tumor vascular architecture

Cited by 58 publications

References 27 publications

Sprouting and intussusceptive angiogenesis in postpneumonectomy lung growth: mechanisms of alveolar neovascularization

Sprouting and intussusceptive angiogenesis in postpneumonectomy lung growth: mechanisms of alveolar neovascularization

Biologicals and Biosimilars

Adnectin-Targeted Inhibitors: Rationale and Results

Contact Info

Product

Resources

About