Grant: Project Grant

The image of the 'therapeutic missile' commonly used to present targeted drug delivery agents emphasizes precision, control, and efficiency. For the next evolution of cancer treatment, antibody-drug conjugates (ADCs) are a great representative of this concept. ADCs home to tumor cells with exquisite precision and control. However, upon landing on tumor cells, ADCs lose their precision, control, and efficiency for effectively delivering and accumulating the drugs inside the cell. ADCs travel in an intracellular route that is controlled by the cancer cell that transports ADC back outside the cell or respond in ways that kick the delivered drugs out. Without the drugs reaching effective cellular concentrations, cancer cells are able to resist and survive and patients soon relapse and die. We will develop ADCs that take control of their intracellular travel by incorporating our new Canadian technology (ACCUM) that mimics how viruses travel inside the cell. ACCUM attaches easily to ADCs enabling them to take control of their travel, which consists of a more efficient route to deliver their drugs. The result is that ACCUM-empowered ADCs are able to deliver their drugs with better efficiency inside target cancer cells than current ADCs. The increased accumulation has resulted in more effective cancer cell killing. The goal of this project is to further mature this technology for use in patients with invasive bladder cancer (IBC) - a worldwide problem without any life saving medications. We performed a clinical study and discovered a target (IL-5Ra) for IBC and developed rodent models that mimics the growth of human IL-5Ra-IBC. The research experiments designed in this proposal are to optimize conditions for clinical translation by optimizing ACCUM-ADC formulation and IBC cell killing. We will then determine the tumor killing effectiveness in our rodent models. This research will place Canada in an ADC leadership role and provide effective treatment for IBC.