2025 New Treatment Accelerator - A/Prof Peter Janes

A major unmet need for treatment of many cancer types, and particularly pancreatic  cancer, is for therapies that specifically target and kill tumour cells while sparing normal  cells and tissues. This is critical for avoiding unwanted side-effects that occur with  standard chemotherapies, which also impact normal cells. To meet this need, we must  identify targets that are specifically or preferentially found on tumour cells, and drugs  that can bind these targets, to block tumour growth. We employ antibodies, which are  proteins made by immune cells that specifically bind to other proteins. These can be  produced in the laboratory and designed to bind specific targets of interest. They can  either inhibit the function of the target protein, or be used to deliver drugs to kill tumour  cells that have the target protein on their surface. 

We have identified two proteins that are particularly abundant on pancreatic tumour  cells, or on surrounding cells and tissues that support tumour growth, called the  'stroma' (literally mattress), or tumour microenvironment. The stroma is particularly  prominent in pancreatic cancer and is thought to contribute to drug resistance . We  showed that both these proteins are important for tumour growth in laboratory models,  and both are particularly abundant in human pancreatic cancers, correlating with worse  patient prognosis. We have thus made antibodies that specifically bind these proteins.  The first binds an active form of the protein ADAM10, and preferentially binds tumour  cells, while the second antibody binds a protein called EphA3, found particularly on  stromal cells in the tumour microenvironment, but not in normal adult tissues. 

We now wish to attach drugs to our novel antibodies, to create antibody-drug  conjugates (ADCs), to selectively bind and kill pancreatic tumour and stromal cells.  ADCs are at the cutting edge of new cancer therapies, and several ADCs have now been  approved by regulatory agencies like the FDA, with many more in clinical trials. We  propose to compare different types of ADCs using our antibodies, to determine their  effectiveness, specificity and safety in laboratory models of pancreatic cancer. We will  also test their effects in combination, and their ability to improve response to  established therapies that are currently ineffective. This includes immunotherapies that  stimulate the body's immune system to attack the tumour, which are effective against  some other cancer types, but not for pancreatic cancer. Importantly, both our  antibodies are suitable for use in humans, and one (against EphA3) has been tested in  clinical trials, confirming its safety and its specific targeting to tumours. All the proposed drug conjugates have also been used in the clinic. Thus, results from these  studies, if positive, can be rapidly translated to clinical trials. 

This grant was made possible by Woolworths' Woolies Wheels and Walks in partnership with Tour de Cure.