Advances in materials synthesis have allowed for a multitude of well-defined biocompatible and stealthy nanoparticles of varying shape and size. For the treatment and diagnosis of cancer, these particles are often developed to exploit the enhanced permeability and retention (EPR) effect, but have limited in vivo efficacy due to their poor retention in tumour tissue. Addition of active targeting ligands with strong binding potentials to membrane receptors uniquely present on malignant cells have shown significant promise towards increasing the retention of nanoparticles in vivo. Many targeting vectors have been explored with some of the most promising types being antibodies; however, conjugation of these antibodies to the nanoparticles (NPs) using traditional chemistries is challenging and conditions can easily change per system. An ideal targeting system would be applicable to multiple types of NPs using a singular conjugation methodology. The Thurecht group and colleagues have prepared a library of a bispecific antibody (BsAb) targeting vectors that have strong binding to a variety of cell-surface receptors commonly overexpressed on cancer cells (EGFR, EphA2, J591, and more), with another antibody specific towards methyl-terminated poly(ethyelene) glycol (PEG) at its distal end.
We have applied this BsAb technology in various diagnostic and/or therapeutic applications in mice and canines with a variety of targets and across multiple diseases. It has shown to be an optimal technology for precision medicine too and is in the process of being applied in comparative oncology and translational studies.