Mohamed A. Alfaleh*, Martina L. Jones*, Christopher B. Howard & Stephen M. Mahler

 

Corner College and Cooper Rds (Bldg 75)
Australian Institute for Bioengineering and Nanotechnology (AIBN)
The University of Queensland
Brisbane, Qld 4072 Australia

 

Human malignant mesothelioma is a chemoresistant tumour that develops from mesothelial cells, commonly associated with asbestos exposure. Malignant mesothelioma incidence rates in European countries are still rising and Australia has one of the highest burdens of malignant mesothelioma on a population basis in the world. Therapy using systemic delivery of free cytotoxic agents is associated with many undesirable side effects due to non-selectivity, and is thus dose-limited which limits its therapeutic potential. Thus, increasing the selectivity of anti-cancer agents will dramatically enhance the drug efficacy and reduce their toxicity. EnGeneIC Dream Vectors (EDV) are antibody-targeted nanocells which can be loaded with cytotoxic drugs and delivered to specific cancer cells via bispecific antibodies (BsAbs) which target the EDV and a cancer cell specific receptor. BsAbs were designed to target doxorubicin-loaded EDVs to cancer cells via cell surface mesothelin (MSLN). Flow cytometry was used to investigate cell binding and induction of apoptosis, and confocal microscopy to visualize internalization. Mouse xenograft models were used to assess anti-tumour effects in vivo, followed by immunohistochemistry for ex vivo evaluation of proliferation and necrosis. BsAb-targeted, doxorubicin-loaded EDVs were able to bind to and internalize into mesothelioma cells in vitro via MSLN receptors and induce apoptosis. In mice xenografts, the BsAb-targeted, doxorubicin-loaded EDVs suppressed the tumour growth and also decreased cell proliferation. Thus, the use of MSLN specific antibodies to deliver an encapsulated doxorubicin can provide a novel and alternative modality for treatment of mesothelioma.

Figure 1: Schematic representation showing the mechanism of Anti-MSLN-BsAbEDVDox nanocell mediated intracellular doxorubicin delivery

 

Biographic Details

Mr. Mohamed Ahmed M Alfaleh

Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD, 4072, Australia.

Faculty of Pharmacy; King Abdulaziz University, Jeddah, 21589, Saudi Arabia

E-mail: mohamed.alfaleh@uqconnect.edu.au

Research interests: phage dispaly, monoclonal antibody, cancer

Venue

Room: 
Hawken N201