Inhibition of placenta growth factor with TB-403: a novel antiangiogenic cancer therapy

Nielsen, Dorte; Sengeløv, Lisa

doi:10.1517/14712598.2012.679655

Cited by 12 publications

(9 citation statements)

References 80 publications

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“…We treated established tumors with TB403, a dual blocking antibody for human and murine PlGF from Roche (Nielsen and Sengelov, 2012). TB403 (αPlGF [R]) treatment led to inhibition of primary tumor growth and spinal metastasis (Figure 2A–B, and Supplemental Figure S1D).…”

Section: Resultsmentioning

confidence: 99%

Targeting Placental Growth Factor/Neuropilin 1 Pathway Inhibits Growth and Spread of Medulloblastoma

Snuderl

Batista

Kirkpatrick

et al. 2013

Cell

212

189

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SUMMARY Medulloblastoma is the most common pediatric malignant brain tumor. Although current therapies improve survival, these regimens are highly toxic and associated with significant morbidity. Here, we report that placental growth factor (PlGF) is expressed in the majority of medulloblastomas independent of their subtype. Moreover, high expression of PlGF receptor neuropilin 1 (Nrp1) correlates with poor overall survival in patients. We demonstrate that PlGF and Nrp1 are required for the growth and spread of medulloblastoma: PlGF/Nrp1 blockade results in direct antitumor effects in vivo, resulting in medulloblastoma regression, decreased metastases, and increased mouse survival. We reveal that PlGF is produced in the cerebellar stroma via tumor-derived Sonic hedgehog (Shh) and show that PlGF acts through Nrp1—and not vascular endothelial growth factor receptor 1 (VEGFR1)—to promote tumor cell survival. This critical tumor-stroma interaction—mediated by Shh, PlGF, and Nrp1 across medulloblastoma subtypes—supports the development of therapies targeting PlGF/Nrp1 pathway.

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Section: Resultsmentioning

confidence: 99%

Targeting Placental Growth Factor/Neuropilin 1 Pathway Inhibits Growth and Spread of Medulloblastoma

Snuderl

Batista

Kirkpatrick

et al. 2013

Cell

212

189

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“…Regarding mAbs against the selective VEGFR-1 ligand PlGF, the humanized recombinant TB-403 (RO5323441) mAb, recognizes the receptor-binding site of the human and murine growth factor [290]. Significant tumor growth inhibition has been observed with TB-403 in medulloblastoma [53], hepatocellular carcinoma and renal cancer [291] xenograft models.…”

Section: Currently Approved Antiangiogenic Therapies and Experimentalmentioning

confidence: 99%

Role of VEGFs/VEGFR-1 Signaling and Its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models

Ceci

Atzori

Lacal

et al. 2020

IJMS

162

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The vascular endothelial growth factor (VEGF) family members, VEGF-A, placenta growth factor (PlGF), and to a lesser extent VEGF-B, play an essential role in tumor-associated angiogenesis, tissue infiltration, and metastasis formation. Although VEGF-A can activate both VEGFR-1 and VEGFR-2 membrane receptors, PlGF and VEGF-B exclusively interact with VEGFR-1. Differently from VEGFR-2, which is involved both in physiological and pathological angiogenesis, in the adult VEGFR-1 is required only for pathological angiogenesis. Besides this role in tumor endothelium, ligand-mediated stimulation of VEGFR-1 expressed in tumor cells may directly induce cell chemotaxis and extracellular matrix invasion. Furthermore, VEGFR-1 activation in myeloid progenitors and tumor-associated macrophages favors cancer immune escape through the release of immunosuppressive cytokines. These properties have prompted a number of preclinical and clinical studies to analyze VEGFR-1 involvement in the metastatic process. The aim of the present review is to highlight the contribution of VEGFs/VEGFR-1 signaling in the progression of different tumor types and to provide an overview of the therapeutic approaches targeting VEGFR-1 currently under investigation.

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“…PlGF knockout mice survive healthy normally with intact vascular system [57] . However, the true potential for anti-PlGF as a therapeutic remedy in inhibiting intratumoral angiogenesis is questionable because it shares the same receptors with the hallmark angiogenic agent, VEGF [58] .…”

Section: Different Angiogenic Pathways Targeted/potentially Targeted mentioning

confidence: 99%

Anti-angiogenic agents for the treatment of solid tumors: Potential pathways, therapy and current strategies – A review

Al‐Abd

Alamoudi

Abdel-Naim

et al. 2017

Journal of Advanced Research

156

122

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Inhibition of placenta growth factor with TB-403: a novel antiangiogenic cancer therapy

Cited by 12 publications

References 80 publications

Targeting Placental Growth Factor/Neuropilin 1 Pathway Inhibits Growth and Spread of Medulloblastoma

Targeting Placental Growth Factor/Neuropilin 1 Pathway Inhibits Growth and Spread of Medulloblastoma

Role of VEGFs/VEGFR-1 Signaling and Its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models

Anti-angiogenic agents for the treatment of solid tumors: Potential pathways, therapy and current strategies – A review

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