“Antimyeloangiogenic” Therapy for Cancer by Inhibiting PlGF

Loges, Sonja; Schmidt, Thomas; Carmeliet, Peter

doi:10.1158/1078-0432.ccr-08-2276

Cited by 59 publications

(48 citation statements)

References 70 publications

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“…PlGF promotes the recruitment and differentiation of bone marrow progenitors and regulates hematopoietic reconstitution after myelosuppression (Hattori et al 2002;Luttun et al 2002;Carlo-Stella et al 2007;Loges et al 2009). PlGF is released by erythroid cells and plasma PlGF is elevated in patients with sickle cell disease (SCD), correlating with hemolysis (Patel et al 2008;Brittain et al 2010).…”

Section: Hematological Homeostasis and Malignanciesmentioning

confidence: 99%

PlGF: A Multitasking Cytokine with Disease-Restricted Activity

Dewerchin¹,

Carmeliet²

2012

Cold Spring Harbor Perspectives in Medicine

194

176

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Section: Hematological Homeostasis and Malignanciesmentioning

confidence: 99%

PlGF: A Multitasking Cytokine with Disease-Restricted Activity

Dewerchin¹,

Carmeliet²

2012

Cold Spring Harbor Perspectives in Medicine

194

176

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“…Multitargeted tyrosine kinase inhibitors such as sorafenib and sunitinib are Food and Drug Administration-approved but do not selectively interfere solely with the PlGF pathways, as they also have activity against the PDGF, VEGFR2, Flt3, and c-kit pathways (11). TB-403 is a monoclonal antibody against PlGF and is currently in phase I clinical trials (26,47). Aflibercept that most closely resembles sFLT01 in (48).…”

Section: Discussionmentioning

confidence: 99%

“…VEGF-A and PlGF levels increased following sunitinib treatment in patients with bevacizumab-refractory metastatic RCC and in men with advanced prostate cancer who were treated with sunitinib (24,25). Thus, PlGF may have a role in resistance to certain antiangiogenic therapies and its neutralization may overcome resistance to VEGF receptor inhibitors (26).…”

Section: Introductionmentioning

confidence: 99%

sFLT01: A Novel Fusion Protein with Antiangiogenic Activity

Kurtzberg¹,

Weber²,

Nguyen³

et al. 2011

Molecular Cancer Therapeutics

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AbstractsFLT01 is a novel fusion protein that consists of the VEGF/PlGF (placental growth factor) binding domain of human VEGFR1/Flt-1 (hVEGFR1) fused to the Fc portion of human IgG 1 through a polyglycine linker. It binds to both human VEGF (hVEGF) and human PlGF (hPlGF) and to mouse VEGF (mVEGF) and mouse PlGF (mPlGF). In vitro, sFLT01 inhibited the proliferation of human umbilical vein endothelial cells and pericytes stimulated by either hVEGF or hPlGF. In vivo, sFLT01 had robust and significant antitumor activity in numerous preclinical subcutaneous tumor models including H460 non-small cell lung carcinoma, HT29 colon carcinoma, Karpas 299 lymphoma, MOLM-13 AML (acute myeloid leukemia), 786-O, and RENCA renal cell carcinoma (RCC). sFLT01 also increased median survival in the orthotopic RENCA RCC model. sFLT01 had strong antiangiogenic activity and altered intratumoral microvessel density, blood vessel lumen size and perimeter, and vascular and vessel areas in RCC models. sFLT01 treatment resulted in fewer endothelial cells and pericytes within the tumor microenvironment. sFLT01 in combination with cyclophosphamide resulted in greater inhibition of tumor growth than either agent used alone as a monotherapy in the A673 Ewing's sarcoma model. Gene expression profiling indicated that the molecular changes in the A673 sarcoma tumors are similar to changes observed under hypoxic conditions. sFLT01 is an innovative fusion protein that possessed robust antitumor and antiangiogenic activities in preclinical cancer models. It is a dual targeting agent that neutralizes both VEGF and PlGF and, therefore, has potential as a next generation antiangiogenic therapeutic for oncology. Mol Cancer Ther; 10(3); 404-15. Ó2011 AACR.

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“…Besides, once a tumor is established, cancer cells promote a constant influx of myelomonocytic cells that express inflammatory mediators supporting pro-tumoral functions. In this regard, myelomonocytic cells are key orchestrators of cancer-related inflammatory processes supporting proliferation and survival of malignant cells, subversion of adaptive immune responses, stromal remodeling and angiogenesis (David Dong et al, 2009;Loges et al, 2009;Porta et al, 2009).…”

Section: Cross-talk Between Inflammation and Angiogenic Growth Factorsmentioning

confidence: 99%