Assessment of an scFv Antibody Fragment Against ELTD1 in a G55 Glioblastoma Xenograft Model
| Autor: | Tanvi Saran, Junho Chung, Debra Saunders, James Battiste, Megan R. Lerner, Michelle Zalles, Kyusang Hwang, Junyeong Jin, Rafal Gulej, Lincy Thomas, Kar Ming Fung, Nataliya Smith, Rheal A. Towner |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Original article Cancer Research medicine.drug_class Angiogenesis Brain tumor Monoclonal antibody lcsh:RC254-282 ELTD1 03 medical and health sciences 0302 clinical medicine In vivo Glioblastoma (GBM) Glioma medicine medicine.diagnostic_test biology business.industry single chain variable fragment (scFv) Magnetic resonance imaging lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Orthotopic G55 xenograft model 3. Good health 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research biology.protein Biomarker (medicine) Antibody business MRI |
| Zdroj: | Translational Oncology, Vol 13, Iss 3, Pp-(2020) Translational Oncology |
| ISSN: | 1936-5233 |
| DOI: | 10.1016/j.tranon.2019.12.009 |
| Popis: | Glioblastoma (GBM), the most common primary brain tumor found in adults, is extremely aggressive. These high-grade gliomas, which are very diffuse, highly vascular, and invasive, undergo unregulated vascular angiogenesis. Despite available treatments, the median survival for patients is dismal. ELTD1 (EGF, latrophilin, and 7 transmembrane domain containing protein 1) is an angiogenic biomarker highly expressed in human high-grade gliomas. Recent studies have demonstrated that the blood-brain barrier, as well as the blood-tumor barrier, is not equally disrupted in GBM patients. This study therefore aimed to optimize an antibody treatment against ELTD1 using a smaller scFv fragment of a monoclonal antibody that binds against the external region of ELTD1 in a G55 glioma xenograft glioma preclinical model. Morphological magnetic resonance imaging (MRI) was used to determine tumor volumes and quantify perfusion rates. We also assessed percent survival following tumor postdetection. Tumor tissue was also assessed to confirm and quantify the presence of the ELTD1 scFv molecular targeted MRI probe, as well as microvessel density and Notch1 levels. In addition, we used molecular-targeted MRI to localize our antibodies in vivo. This approach showed that our scFv antibody attached-molecular MRI probe was effective in targeting and localizing diffuse tumor regions. Through this analysis, we determined that our anti-ELTD1 scFv antibody treatments were successful in increasing survival, decreasing tumor volumes, and normalizing vascular perfusion and Notch1 levels within tumor regions. This study demonstrates that our scFv fragment antibody against ELTD1 may be useful and potential antiangiogenic treatments against GBM. Keywords: Glioblastoma (GBM), ELTD1, Angiogenesis, Orthotopic G55 xenograft model, MRI, single chain variable fragment (scFv) |
| Databáze: | OpenAIRE |
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