Peter Mac scientists who are pioneering new treatments and advancing understanding of cancer have secured more than $10 million funding from the National Health and Medical Research Council (NHMRC).
The newly funded projects include efforts to take CAR T-cell therapy – so far a breakthrough treatment in blood cancers – and apply this to solid tumours, and other novel approaches which seek to harness the patient’s immune system as a powerfully ally to fight their cancer.
Other funded projects will improve understanding the root cause of Barret’s oesophagus - a precursor to throat cancer, test new epigenetic approaches to treating blood cancers, and also determine how best to treat secondary cancers that have spread to bone.
The NHMRC is the nation’s premier scientific funding body and recipients of its latest “Ideas Grants” were announced this week. This highly competitive grants program is focused on early to mid-career scientists, and supports innovative health and medical research from fundamental discoveries through to clinical trials and implementation.
Peter Mac’s Executive Director of Cancer Research, Professor Ricky Johnstone, said it was fantastic to see the new NHMRC funding directed towards discovery-based and translational science at Peter Mac.
“This is an excellent result overall and speaks to the wide pipeline of innovative cancer research underway at Peter Mac across a range of scientific disciplines,” Professor Johnstone says.
“Congratulations to all of our latest grants recipients, and I’d like to give a special shout-out to Dr Jennifer Devlin and Dr Pilar Dominguez who are both relatively early-career applicants and can use these grants as a springboard for their academic careers.”
In all, ten Peter Mac projects were successful and these received a combined $10,516,956 in this round of funding. All of the successful projects are summarised below:
1. Associate Professor Paul Neeson – Targeting cold tumours with triple therapy ($1.62M)
Patients with advanced metastatic disease have a very poor clinical outcome and are the main group of patients with an unmet clinical need. We know that very advanced cancers are resistant to the patient's immune system, and immune based therapies. In my program I will address these issues by (1) revealing how the patient's cancer avoids the immune system (2) create new types of T cells which will be resistant to the tumour immune evasion mechanisms (3) translate my findings into the clinic.
2. Associate Professor Ilia Voskoboinik – Cytotoxic T cell granules “a matter of life and death” ($1.38M)
Humans are protected from infections and cancer by a subset of immune cells called cytotoxic lymphocytes, which can recognised and kill rogue cells. Despite an enormous clinical interest, how these cells mature from a naive inactive to a fully activated state is poorly understood. The aim of the current proposal is to investigate that process, and thus provide a better understanding of how the immune system works and how it can be better utilised to treat cancer and other diseases.
3. Professor Wayne Phillips - Submucosal glands as the origin of Barretts oesophagus and oesophageal adenocarcinoma ($1.11M)
Barrett’s oesophagus is a relatively common benign condition that arises as a consequence of acid reflux. In some patients, Barrett’s progresses to oesophageal cancer, for which treatments are largely ineffective and thus outcomes are poor. This project addresses a vital gap in our knowledge regarding the cell of origin of Barrett’s oesophagus, which will enable the future development of effective strategies for early intervention or prevention of oesophageal cancer.
4. Dr Maria del Pilar Dominguez Rodriguez - Targeting deregulated epigenetic mechanisms in lymphoma ($1.11M)
Diffuse large B-cell lymphomas (DLBCL) are aggressive tumors, with 40% patients not responding to the conventional chemotherapy treatment or relapsing after treatment. In this proposal, we will evaluate new epigenetic therapies to treat these lymphomas, targeting the non-inherited environmental factors that control the function of genes. We predict that the results from this project will drive new clinical trials for DLBCL patients with TET2 or CREBBP mutations, which represent 1 in 3 patients.
5. Dr Kristin Brown - Investigating the role of cellular metabolism in regulating antigen presentation and tumour immune escape ($994K)
In order to develop and progress, tumours must avoid elimination by the immune system. Understanding the mechanisms that allow tumours to evade the immune system is critical for developing strategies to overcome immune escape and enhance the efficacy of currently existing immunotherapies. This research will investigate the fundamental mechanisms by which aberrant cell metabolism contributes to immune evasion in cancer and identify strategies to restore tumour elimination by the immune system.
6. Associate Professor Paul Beavis - Engineering chimeric antigen receptor (CAR) T cells that induce host anti-tumour immunity ($984K)
7. Associate Professor Paul Beavis - CRISPR Engineering of CAR T Cells to Enhance Efficacy in Solid Tumours ($897K)
Both of these projects will further enhance the therapeutic application of a gene-engineering based immune therapy involving a patients' own cells. To date this form of therapy has been effective in blood cancers but not solid tumours. We will aim to overcome this by developing technological and scientific advances which will make the immune cells more effective against solid tumours. These findings have the potential to provide treatment options for late stage solid tumour cancer patients.
8. Dr Jennifer Devlin - Targeting dysregulated transcription in cancer through Cyclin-Dependent-Kinase 11 ($849K)
Many proteins cooperate to carefully control which genes are ‘on’ or ‘off’ in our cells. Defects in gene control that cause cells to grow faster and to live longer than normal give rise to cancer. I will investigate the activity of a group of proteins called Cyclin-dependent-kinases (CDKs), that are essential for ensuring proper gene control and are essential for cancer cells to survive. This will allow us to design better strategies to block the activity of CDKs to kill cancer cells.
9. Associate Professor Belinda Parker - Boosting cellular immunogenicity to combat metastatic cancer ($658K)
Spread (metastasis) to bone in breast and prostate cancer is painful and very difficult to treat. We have discovered that cancers growing in bone have developed changes to allow them to go undetected and escape immune control. In this proposal, we will discover ways to reverse these changes and increase response to radiotherapy and immune therapies to target deadly metastatic cancers. This work will offer a new avenue of therapy for bone metastasis that is built on strong biological discoveries.
10. Associate Professor Louise Cheng - Identification of metabolic alterations in cancer cachexia ($894K)
Cachexia is a metabolic disease where tumours cause muscle and fat to waste away. We established a Drosophila (fruit fly) model of cachexia-like wasting, opening up a novel opportunity to use its powerful genetic tools to better understand the genetic basis of cachexia-like wasting. This grant proposes to look at how organs can communicate with each other, and our findings will allow us to find potential new avenues for the development of treatment strategies for cachexia.
For more information on NHMRC funding rounds, check their website.