Overseas grant pivotal to scientist’s immune therapy project

Associate Professor Meredith O'Keeffe
Associate Professor Meredith O'Keeffe

Expertise, 20 years of experience in her field and a left-of-field idea have helped Monash Biomedicine Discovery Institute (BDI) Associate Professor Meredith O’Keeffe gain a $500,000 Worldwide Cancer Research grant.

The grant, spread over three years and co-funded by Cancer Australia, will allow Associate Professor O’Keeffe to pursue an innovative project investigating the role of dendritic cells in the immune system.

Understanding how these cells might be used to help kill tumour cells could potentially lead to improved immunotherapies.

“Immune therapies have been amazingly successful in clinics for certain cancers but even in the best case scenario – in melanoma where they work for 40 per cent of people – they don’t work for the rest of the people and we don't understand why,” Associate Professor O’Keeffe said.

“My lab believes that understanding the precise function of dendritic cells will help us to improve future therapies.”

The role that dendritic cells, the sentinels of the immune system, play in immunotherapy currently isn’t known, she said.

Associate Professor O’Keeffe and her team will test the effect of a new type of immunotherapy called checkpoint inhibitors on dendritic cells. Checkpoint inhibitors, which are generating excitement in, particularly, skin cancer research, turn off the brakes on cells of the immune system, enabling them to better kill tumour cells.

“Immunotherapies are designed to awaken T cells – the killer cells of the immune system – which are inactivated in the tumour environment,” Associate Professor O’Keeffe said.

“They do that by expressing these particular molecules on the cell surface. Stopping the expression of these molecules leads to turning off these activating signals,” she said.

“Quite by accident we found that dendritic cells also express these molecules that can turn off activation. The molecules are thought to be expressed only on T cells.”

“We think that when immunotherapy is used in vivo that part of the reason it works is that it is also hitting the dendritic cells as well as T cells – and that hasn’t been examined before,” she said.

Associate Professor O’Keeffe said the grant would enable former PhD student in the lab, Ee Shan Pang, to continue work on the project and will fund laboratory costs. “It’s fantastic,” she said. “This grant really has made the world of difference to doing this work.”

Ee Shan’s PhD work together with work of former post-doc Christophe Macri (now at the University of Melbourne) and former PhD student Ben Fancke (now at NeoGenomics Laboratories, Switzerland) provided the preliminary data that was used in the grant application.

“It’s fantastic that Ee Shan will be able to kick-start her post-doctoral career and do that work for the next few years,” Associate Professor O’Keeffe said.

The BDI scientists will collaborate with co-investigator Professor Mark Shackleton and his laboratory at the Alfred Hospital on the research.


About the Monash Biomedicine Discovery Institute

Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.