Poster Presentation 29th Lorne Cancer Conference 2017

Development of a therapeutic modality for the specific treatment of EpCAM positive brain metastases (#213)

Joanna Macdonald 1 , Wei Duan 1 , Sarah Shigdar 1
  1. School of Medicine, Deakin University, Waurn Ponds, VIC, Australia

Affecting approximately 25% of all cancer patients following primary malignancy treatment, the prognosis for patients suffering from metastatic brain tumours is very poor. The treatment of these metastatic tumours is greatly hindered by the presence of the blood brain barrier which restricts the overwhelming majority of small molecules from entering the brain. A novel approach in which to overcome this barrier is to target receptor mediated transport mechanisms present on the endothelial cell membranes, in particular the transferrin receptor. Given their specificity, safety profile and stability, nucleic acid based therapeutics are ideal for this purpose. Therefore, in this study an aptamer targeting the transferrin receptor was fused with an aptamer that binds to epithelial cell adhesion molecule-expressing cancer cells. The initial fusion of the two sequences enhanced the binding affinity of both aptamers while maintaining specificity, which was confirmed through flow cytometry and confocal microscopy. Using an in vitro blood brain barrier model, the aptamers ability to transcytose the barrier and target a specific population of cells was confirmed through the implementation of a co-culture of EpCAM positive and negative cells. Subsequent to this, we confirmed the aptamers ability to transcytose the blood brain barrier in a healthy mouse model following a single i.v. injection (40 nmol/kg). These promising results demonstrate that through the fusion of two aptamer sequences, a bi-functional aptamer can be generated which has the potential to be developed for the specific treatment of EpCAM positive brain metastases.