EXTH-07. OPTIMIZATION OF TARGETING ELTD1 IN GLIOBLASTOMA USING A MOLECULAR TARGETING APPROACH

The standard of care for glioblastoma multiform (GBM), an aggressive form of cancer, has not significantly increased the prognosis for patients. ELTD1 (epidermal growth factor, latrophilin, and 7 transmembrane domain containing protein 1), a biomarker for angiogenesis, was found to be highly expressed in human high-grade gliomas. Novel treatments targeting ELTD1 with polyclonal (pAb) and monoclonal (mAb) antibodies were effective as a potential cancer therapy in a G55-xenograft mouse model. While our studies have demonstrated that the blood brain barrier (BBB) was leaky around the tumor region, other studies have shown that the BBB is not equally disrupted in GBM patients, therefore suggesting that the mAb may have difficulty crossing the BBB and infiltrating the tumor due to its size. To overcome these limitations, this study focused on the optimization of targeting ELTD1 by using an optimized svFc antibody fragment derived from our mAb against ELTD1. Immunocompromised mice were intracerebrally injected with human-G55 cells. Morphological MRI was used to monitor and calculate tumor volumes. Treatments using IgG, anti-ELDT1 mAb or fragment upon tumor detection. Vascular perfusion images were obtained to examine vascular alterations. Molecular targeting imaging (mtMRI) was conducted to assess the binding specificity of our antibodies against the tumor region. Targeting ELTD1 with varying antibodies (anti-ELTD1 mAb and scFv fragment) resulted in increased survival and decreased tumor volumes in a G55 xenograft GBM mouse model. Additionally, through the use of mtMRI, we determined altered levels of binding specificity against the tumor region using three different anti-ELTD1 attached probes (monoclonal and scFv fragment antibodies). Our data suggest that the optimization of an anti-ELTD1 therapy could be used to better target angiogenesis in glioblastomas.

Development of Antibody-Coated Magnetite Nanoparticles for Biomarker Immobilization

Magnetic nanoparticles (MNPs) have great potential in biomedical applications because of their magnetic response offers the possibility to direct them to specific areas and target biological entities. Magnetic separation of biomolecules is one of the most important applications of MNPs because their versatility in detecting cancer biomarkers. However, the effectiveness of this method depends on many factors, including the type of functionalization onto MNPs. Therefore, in this study, magnetite nanoparticles have been developed in order to separate the 5′-nucleotidase enzyme (5eNT). The 5eNT is used as a bio-indicator for diagnosing diseases such as hepatic ischaemia, liver tumor, and hepatotoxic drugs damage. Magnetic nanoparticles were covered in a core/shell type with silica, aminosilane, and a double shell of silica-aminosilane. A ScFv (fragment antibody) and anti-CD73 antibody were attached to the coated nanoparticles in order to separate the enzyme. The magnetic separation of this enzyme with fragment antibody was found to be 28% higher than anti-CD73 antibody and the enzyme adsorption was improved with the double shell due to the increased length of the polymeric chain. Magnetite nanoparticles with a double shell (silica-aminosilane) were also found to be more sensitive than magnetite with a single shell in the detection of biomarkers.