@article{2ea556fcec0945efbfdf01ed2dd7625e,
title = "Optimized monoclonal antibody treatment against ELTD1 for GBM in a G55 xenograft mouse model",
abstract = "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.",
keywords = "ELTD1, MRI, angiogenesis, glioblastoma (GBM), molecular-targeted MRI, monoclonal antibody (mAb), notch, orthotopic G55 xenograft model, relative cerebral blood flow (rCBF)",
author = "Michelle Zalles and Nataliya Smith and Jadith Ziegler and Debra Saunders and Shannon Remerowski and Lincy Thomas and Rafal Gulej and Nadya Mamedova and Megan Lerner and Fung, {Kar Ming} and Junho Chung and Kyusang Hwang and Junyeong Jin and Graham Wiley and Chase Brown and James Battiste and Wren, {Jonathan D.} and Towner, {Rheal A.}",
note = "Funding Information: This work was supported in part by the Oklahoma Medical Research Foundation (RT) and the Seoul National University Foundation (JC); National Institutes of Health (1S10OD023508-01 to RT, 2P20GM103636 to JW). Whole slide scanning and image analysis are kindly provided by Peggy and Charles Stephenson Cancer Center at the University of Oklahoma Health Sciences Center, Oklahoma City, OK, an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences (P20 GM103639) and a Cancer Center Supporting Grant Award from the National Cancer Institute (P30 CA225520). MZ performed the research and wrote the manuscript. The manuscript was edited by RT, NS, DS, JW, JC and RG. JZ, DS and SR assisted during the animal surgery. MR imaging and treatment were conducted by MZ, JZ, NS, DS, SR, LT and RG. Molecular-targeted MR imaging and RNA isolation were conducted by NS and MZ. JC, KH and JJ generated the anti-ELTD1 monoclonal antibody. MZ, ML, KMF and JC performed and assisted with the IHC and analysis. JW and CB performed RNA-seq and bioinformatics analyzes. MZ and SR analysed the MRI data. RT was the principle investigator. Funding Information: This work was supported in part by the Oklahoma Medical Research Foundation (RT) and the Seoul National University Foundation (JC); National Institutes of Health (1S10OD023508‐01 to RT, 2P20GM103636 to JW). Whole slide scanning and image analysis are kindly provided by Peggy and Charles Stephenson Cancer Center at the University of Oklahoma Health Sciences Center, Oklahoma City, OK, an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences (P20 GM103639) and a Cancer Center Supporting Grant Award from the National Cancer Institute (P30 CA225520). MZ performed the research and wrote the manuscript. The manuscript was edited by RT, NS, DS, JW, JC and RG. JZ, DS and SR assisted during the animal surgery. MR imaging and treatment were conducted by MZ, JZ, NS, DS, SR, LT and RG. Molecular‐targeted MR imaging and RNA isolation were conducted by NS and MZ. JC, KH and JJ generated the anti‐ELTD1 monoclonal antibody. MZ, ML, KMF and JC performed and assisted with the IHC and analysis. JW and CB performed RNA‐seq and bioinformatics analyzes. MZ and SR analysed the MRI data. RT was the principle investigator. Publisher Copyright: {\textcopyright} 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicineand John Wiley & Sons Ltd.",
year = "2020",
month = jan,
day = "1",
doi = "10.1111/jcmm.14867",
language = "English (US)",
volume = "24",
pages = "1738--1749",
journal = "Journal of Cellular and Molecular Medicine",
issn = "1582-1838",
publisher = "Wiley-Blackwell",
number = "2",
}