A novel, highly specific anti-cancer dual-payload targeted-delivery platform

Pancreatic cancer and triple-negative breast cancer (TNBC) are very difficult to treat and have a poor prognosis. Both cancers overexpress the epidermal growth factor receptor (EGFR) and the hepatocellular tyrosine kinase class A2 (EphA2) – two receptor tyrosine kinases (RTKs) that show functional cross-talk and, if inhibited simultaneously, can overcome the acquired resistance to monotherapy.

We develop a novel, ‎antibody-guided dual-payload delivery system that consist of (I) recombinant bi-specific antibody (bsAb), termed anti-EGFR/EphA2, which simultaneously binds EGFR and EphA2 and enters the cells via receptor-mediated endocytosis; (II) dual combination of the anti-cancer drugs and (III) the fluorescent real-time monitoring system.

Our in vitro experiments showed that using similar, low-nanomolar concentrations of the antimitotic agent dolastatinol and the chimeric DNA methylating topoisomerase 1 (Top1) inhibitor, SN38Me, induces synergistic effects in killing cancer cells. Our in vivo experiments using Fluorescence Imaging Tomography (FLIT) showed high targeting specificity of the researched bsAb in TNBC MDA-MB-468 xenograft model.

The expected outcome of the study is a novel, highly specific dual-payload targeted-delivery platform, which could later be used with a wide range of antibodies and drugs aimed at different targets and for various purposes.