Optimized monoclonal antibody treatment against ELTD1 for GBM in a G55 xenograft mouse model

Autor: Chase A. Brown, Kar Ming Fung, Nataliya Smith, Shannon Remerowski, Debra Saunders, Junyeong Jin, Michelle Zalles, Rheal A. Towner, Graham B. Wiley, Nadya Mamedova, Rafal Gulej, Kyusang Hwang, James Battiste, Megan R. Lerner, Junho Chung, Jadith Ziegler, Lincy Thomas, Jonathan D. Wren
Rok vydání: 2019
Předmět:
0301 basic medicine
medicine.drug_class
Angiogenesis
Monoclonal antibody
ELTD1
Receptors
G-Protein-Coupled
angiogenesis
Mice
03 medical and health sciences
0302 clinical medicine
Cell Line
Tumor
Glioma
medicine
Animals
Humans
orthotopic G55 xenograft model
Receptors
Notch
biology
Brain Neoplasms
business.industry
Antibodies
Monoclonal
Original Articles
Cell Biology
medicine.disease
Xenograft Model Antitumor Assays
Tumor Burden
3. Good health
molecular‐targeted MRI
030104 developmental biology
Polyclonal antibodies
030220 oncology & carcinogenesis
Microvessels
Monoclonal
biology.protein
Cancer research
Molecular Medicine
Immunohistochemistry
Biomarker (medicine)
Original Article
glioblastoma (GBM)
monoclonal antibody (mAb)
relative cerebral blood flow (rCBF)
Antibody
Glioblastoma
business
Chickens
MRI
notch
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
1582-1838
DOI: 10.1111/jcmm.14867
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: