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A potential mechanism to improve targeted immuno-therapies and immune-cell / tumour cell interaction
5th Asia Pacific Global Summit and Expo on Vaccines & Vaccination
July 27-29, 2015 Brisbane, Australia
Fiona Simpson
Posters-Accepted Abstracts: J Vaccines Vaccin
Abstract:
Monoclonal antibodies are emerging as an important component of cancer treatment regimes. However, clinical outcomes can be unpredictable and the biological determinants of antibody therapy sensitivity remain unknown. For example, it is unclear why a patient, whose tumour over-expresses the Epidermal Growth Factor Receptor (EGFR), does not respond to therapeutic antibodies directed against EGFR. We have developed a novel imaging method that allows ex-vivo examination and quantification of ligand-induced endocytosis of EGFR in non-dissociated human squamous cell carcinoma (SCC). Using confocal, three dimensional structured illumination microscopy (3D-SIM) and multi-parametric fluorescence activated cell sorting (FACS) analysis we have demonstrated that receptor trafficking influences antibody-dependent cellular cytotoxicity and that blocking receptor trafficking can enhance anti-EGFR antibody (Cetuximab)-induced SCC tumour cell death by ADCC in Cetuximab-insensitive SCC cells. Using different classes of endocytosis inhibitors we are able to demonstrate that ADCC increase occurs only when the surface EGFR is clustered and this presents a new model for targeted therapy.