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ELTD1, an effective anti-angiogenic target for gliomas: preclinical assessment in mouse GL261 and human G55 xenograft glioma models.

Authors: Ziegler, Jadith  Pody, Richard  Coutinho de Souza, Patricia  Evans, Blake  Saunders, Debra  Smith, Nataliya  Mallory, Samantha  Njoku, Charity  Dong, Yunzhou  Chen, Hong  Dong, Jiali  Lerner, Megan  Mian, Osamah  Tummala, Sai  Battiste, James  Fung, Kar-Ming  Wren, Jonathan D  Towner, Rheal A 
Citation: Ziegler J, etal., Neuro Oncol. 2017 Feb 1;19(2):175-185. doi: 10.1093/neuonc/now147.
Pubmed: (View Article at PubMed) PMID:27416955
DOI: Full-text: DOI:10.1093/neuonc/now147

Background: Despite current therapies, glioblastoma is a devastating cancer, and validation of effective biomarkers for it will enable better diagnosis and therapeutic intervention for this disease. We recently discovered a new biomarker for high-grade gliomas, ELTD1 (epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1) via bioinformatics, and validated that ELTD1 protein levels are significantly higher in human and rodent gliomas. The focus of this study was to assess the effect on tumor growth of an antibody against ELTD1 in orthotopic, GL261, and G55 xenograft glioma models.
Methods: The effect of anti-ELTD1 antibody therapy was assessed by animal survival, MRI measured tumor volumes, MR angiography, MR perfusion imaging, and immunohistochemistry (IHC) characterization of microvessel density in mouse glioma models. Comparative treatments included anti-vascular endothelial growth factor (VEGF) and anti-c-Met antibody therapies, compared with untreated controls.
Results: Tumor volume and survival data in this study show that antibodies against ELTD1 inhibit glioma growth just as effectively or even more so compared with other therapeutic targets studied, including anti-VEGF antibody therapy. Untreated GL261 or G55 tumors were found to have significantly higher ELTD1 levels (IHC) compared with contralateral normal brain. The anti-angiogenic effect of ELTD1 antibody therapy was observed in assessment of microvessel density, as well as from MR angiography and perfusion measurements, which indicated that anti-ELTD1 antibody therapy significantly decreased vascularization compared with untreated controls.
Conclusions: Either as a single therapy or in conjunction with other therapeutic approaches, anti-ELTD1 antibodies could be a valuable new clinical anti-angiogenic therapeutic for high-grade gliomas.


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CRRD Object Information
CRRD ID: 13838664
Created: 2019-01-08
Species: All species
Last Modified: 2019-01-08
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.