Optimized monoclonal antibody treatment against ELTD1 for GBM in a G55 xenograft mouse model.
Animals
Antibodies, Monoclonal
/ pharmacology
Brain Neoplasms
/ drug therapy
Cell Line, Tumor
Chickens
Glioblastoma
/ drug therapy
Humans
Mice
Microvessels
/ drug effects
Receptors, G-Protein-Coupled
/ immunology
Receptors, Notch
/ metabolism
Tumor Burden
/ drug effects
Xenograft Model Antitumor Assays
ELTD1
MRI
angiogenesis
glioblastoma (GBM)
molecular-targeted MRI
monoclonal antibody (mAb)
notch
orthotopic G55 xenograft model
relative cerebral blood flow (rCBF)
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
25
09
2019
revised:
11
11
2019
accepted:
12
11
2019
pubmed:
22
12
2019
medline:
23
4
2021
entrez:
22
12
2019
Statut:
ppublish
Résumé
Glioblastoma is an aggressive brain tumour found in adults, and the therapeutic approaches available have not significantly increased patient survival. Recently, we discovered that ELTD1, an angiogenic biomarker, is highly expressed in human gliomas. Polyclonal anti-ELTD1 treatments were effective in glioma pre-clinical models, however, pAb binding is potentially promiscuous. Therefore, the aim of this study was to determine the effects of an optimized monoclonal anti-ELTD1 treatment in G55 xenograft glioma models. MRI was used to assess the effects of the treatments on animal survival, tumour volumes, perfusion rates and binding specificity. Immunohistochemistry and histology were conducted to confirm and characterize microvessel density and Notch1 levels, and to locate the molecular probes. RNA-sequencing was used to analyse the effects of the mAb treatment. Our monoclonal anti-ELTD1 treatment significantly increased animal survival, reduced tumour volumes, normalized the vasculature and showed higher binding specificity within the tumour compared with both control- and polyclonal-treated mice. Notch1 positivity staining and RNA-seq results suggested that ELTD1 has the ability to interact with and interrupt Notch1 signalling. Although little is known about ELTD1, particularly about its ligand and pathways, our data suggest that our monoclonal anti-ELTD1 antibody is a promising anti-angiogenic therapeutic in glioblastomas.
Identifiants
pubmed: 31863639
doi: 10.1111/jcmm.14867
pmc: PMC6991683
doi:
Substances chimiques
ADGRL4 protein, human
0
Antibodies, Monoclonal
0
Receptors, G-Protein-Coupled
0
Receptors, Notch
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1738-1749Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103639
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA225520
Pays : United States
Organisme : NIH HHS
ID : S10 OD023508
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103636
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20GM103639
Pays : United States
Informations de copyright
© 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicineand John Wiley & Sons Ltd.
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