Peter Mac researchers working on cures for breast cancer have just been awarded more than $4.5 million in grants from the National Breast Cancer Foundation. Each day 57 women are diagnosed with breast cancer and it remains the second largest cause of cancer death in women.
In a quest to change outcomes for breast cancer the National Breast Cancer Foundation has funded four researchers from Peter Mac so they can explore their novel concepts.
Professor Ricky Johnstone, Executive Director of Cancer Research said “The quality of our breast cancer research proposals was clear with 55 per cent of our submissions receiving funding.
“We thank the National Breast Cancer Foundation for their support and belief in our researchers, we look forward to uncovering new ways to treat this very common cancer.”
Associate Professor Paul Beavis – Genetic engineering of immune cells to treat breast cancer
Associate Professor Beavis will work to redirect a patient’s own immune cells by genetically engineering them with a Chimeric Antigen Receptor (CAR), known as CAR T cell therapy. The CAR allows the immune cells to ‘recognise’ and subsequently kill tumour cells.
This therapy is highly effective in blood cancers however this approach is currently not effective in breast cancer. This is because breast cancer cells can adapt so the protein targeted by the CAR is no longer present and the cancer cells escape detection.
To overcome this, Associate Professor Beavis’ lab have engineered immune cells to express both a CAR and a second factor that activates the host immune system to ‘join’ the attack against the tumour. Associate Professor Beavis explains this approach here.
To improve the efficacy of this treatment further he will engineer immune cells to secrete factors only when they ‘see’ tumour cells so the patient’s immune system is activated locally to kill tumour cells. This should reduce toxicities that affect a patient quality of life and their ability to tolerate the therapy. Ultimately Associate Professor Beavis aspires to transition this to a first in human CAR T cell trial at the Peter Mac.
Professor Riccardo Dolcetti – Targeting novel classes of tumour antigens in BRCA-deficient breast cancer to improve immunotherapy responses and overcome resistance.
The use of the patient’s immune system for the treatment of challenging cancers is providing hope however more research is needed to make these treatments effective for breast cancer. This is particularly relevant for breast cancer caused by the BRCA gene mutation that still have limited therapeutic options.
Therapeutic cancer vaccines are an emerging and promising approach to using immunotherapies to treat breast cancer. This is because the vaccine will generate new immune cells that are able to recognise cancer-specific targets (antigens) and eliminate tumour cells displaying those antigens. The challenge is identifying the right targets.
Professor Dolcetti’s lab have developed new technologies that allow the identification and selection of novel antigens produced by breast cancers with BRCA1/2 mutations or those that don’t have the gene but their cancer behaves like those with the BRCA genes mutated. He will select and test vaccines that display the most “potent” target antigens to look at safety and efficacy ahead of trials in humans.
Associate Professor Belinda Parker – Using hormone targeted drugs to switch on the immune response against cancer.
To make a difference for breast cancer patients, Associate Professor Parker aims to identify hormone-based therapies that, when used at the time of diagnoses, are most likely to prevent subsequent metastatic spread.
Associate Professor Parker’s lab has discovered that specific hormone therapy approaches, including those about to be trialled in the clinic, have the potential to make migrating cancer cells more visible to the immune system. This prepares the body to attack its own cancer before it has the opportunity to spread to other parts of the body, like the bone.
Associate Professor Parker will test a range of standard treatments and alternate hormone therapies to see if they can alter the bone environment to promote cancer cell destruction before the formation of large metastases, when it’s too late to intervene. Her tests will use a novel biology-based screening technology and pre-clinical (including living human tissue) models of metastatic hormone driven cancers.
This work will provide a new approach for prioritising the most promising hormone therapies upfront for standard of care upon diagnosis of hormone driven breast cancer.
Professor Christobel Saunders- kConFab, a resource to facilitate a range of research into familial breast cancer to improve treatments, survivability and risk-reduction options for those at high-risk.
Cancer is due to an inherited gene fault (mutation) for one in 20 people. This puts multiple family members at risk of not just breast, but also ovarian, prostate and pancreatic cancer, often at a young age.
kConFab is a world-class resource that has had a major impact on outcomes for high-risk cancer families through improved cancer prevention strategies, medications and cancer treatments. It collects blood and tissues, clinical, genetic and lifestyle data on 2,132 multi-case breast/ovarian cancer families and makes this resource available for approved research.
kConFab collaborators have discovered breast, ovarian and prostate cancer-causing mutations that have enabled personalised risk-assessment for family members however more needs to be done. There are still many breast cancer families where the mutation causing the cancer is yet to be found.
Professor Saunders, Professor Sherene Loi and the kConFab team under Associate Professor Heather Thorne will use kConFab to further improve what we know about gene mutation carriers and to identify the unexplained genetic causes in nearly half of the high-risk families including:
- gene discovery
- improved screening and early detection biomarkers for cancer prevention/early cancer detection
- develop better cancer treatments and risk reduction strategies including medications
- research into metastatic disease
- research into the lifestyle and molecular genetic causes of not only breast, but also prostate, pancreatic and ovarian cancer
- psychosocial factors that contribute to positive health outcomes for these women and families.
Dr Clare Slaney – Turning COVID-19 induced immunity against breast cancers.
Dr Slaney’s lab has found a way to make CAR T-cells work in the solid tumour setting. Dr Slaney used a vaccine to stimulate CAR T-cells which was extremely effective at eradicating cancers of the breast, sarcoma and colon in mice. However, to translate this to humans, the major hurdle is identifying a potent vaccine that stimulates T cell receptors that will work in most people.
During the COVID-19 pandemic, a number of vaccines were developed, and the majority of the vaccines target the SARS-CoV-2 spike protein. Thus, the spike protein-specific memory T cells are already present in the majority of the world population, either by vaccination, or by infection. These memory T cells can be re-activated and expanded by the spike protein.
Dr Slaney’s lab will try to use SARS-CoV-2-specific memory T cells from vaccinated or COVID-19-recovered patients as a source of CAR T cells (Corona-CAR). They will use a COVID mRNA vaccine to stimulate the Corona-CAR T cells to fight against cancers. If successful, this project will provide a substantial breakthrough in cancer treatment, and translation to the clinic could be achieved in the short term.
