Poster Presentation 29th Lorne Cancer Conference 2017

The functionalization of a DNA chemical antibody targeting EpCAM for the delivery of a common chemotherapeutic agent (#169)

Justin Henri 1
  1. Deakin University, Geelong, VIC, Australia

Current therapy for cancer typically involves indiscriminate chemotherapies that can have severe off target effects on healthy tissue and are still plagued by aggressive recurrence. Recent shifts towards targeted therapies offer the possibility of circumventing the obstacles experienced by these traditional treatments. While antibodies are the pioneering agents in such targeted therapies, clinical experience has demonstrated that their antitumor efficacy is limited due to their high immunogenicity, large molecular size, and costly and laborious in vivo production. In contrast, nucleic based chemical antibodies, also known as aptamers, are ideal for this application given their small size, lack of immunogenicity and in vitro production. This study sought to explore the efficacy of a DNA aptamer, designed to target a well-established cancer biomarker, EpCAM, to deliver a chemotherapeutic drug. By truncating a large DNA EpCAM aptamer, smaller novel aptamers that maintained sensitivity and specificity towards EpCAM were engineered. The ability of these aptamers to be internalised by EpCAM positive cells was demonstrated through confocal microscopy. Specificity was further confirmed with internalisation of these aptamers not being displayed in EpCAM negative cell lines. The ability of the Full Length and truncated aptamers to intercalate doxorubicin (DOX) was characterised. Further optimisation of these aptamers ability to intercalate DOX was also performed through the extension of the non-binding region of the aptamer to increase drug loading. Hence this study has developed DNA EpCAM aptamers that have the exciting prospect of being used as a targeted delivery system for DOX to target cancer cells specifically.‚Äč