Collaborative research projects
Unleashing the potential of immunotherapies for breast cancer
“Breast cancer is the most common cancer in women — yet, for about a third of individuals with breast cancer, treatment options are very limited,” says Dr Gallego- Ortega. “So, there’s an urgent need to explore other treatment options to ensure that those individuals aren’t left behind.”
Immunotherapies, which ‘re-educate’ the immune system to recognise and destroy cancer cells, have achieved exceptional success against some types of cancers, particularly lung cancer and melanoma. In breast cancers, however, immunotherapy has been disappointing — because, in breast tumours, the immune system’s function is ‘dialed down’ and immunotherapies can’t work effectively.
The research team has already uncovered how immune function is stymied in breast cancer in preclinical models. They showed that a particular group of cells, called MDSCs (myeloid derived suppressor cells), accumulate in breast tumours and cripple immune function. Tantalisingly, the team has also shown in preclinical models that they can target and destroy MDSCs, which releases the brake on the immune system to let immunotherapies do their job.
The next step? “It’s time to investigate a similar approach in people. We will define, in unprecedented detail, the cells that make up a human breast tumour, with a particular focus on understanding MDSCs,” says Dr Gallego-Ortega.
Armed with a deep cell-by-cell understanding of human breast cancer, the researchers will explore new ways to knock out MDSCs within tumours by using antibodies that will result in the reactivation of the body’s ability to reject cancer cells. This immunotherapy approach is particularly promising for the deadly triple-negative breast cancer and familial BRCA1/2 mutation carriers.
Ultimately, they aim to identify antibodies that have the power to unleash immunotherapies and transform outcomes for breast cancer patients.
Zeroing in on the cancer cells that 'sleep' in bone
Garvan and Weizmann researchers, led by Professor Peter Croucher, Dr Tri Phan and Professor Ido Amit, are working together to solve why some cancer cells ‘sleep’ in bone for months or even years — and how their genetic output changes as they ‘wake’.
The researchers are studying multiple myeloma, a cancer of the blood in which cells lodge in bone. Already, they have isolated thousands of individual myeloma cells from bone and conducted two different kinds of single-cell analyses to measure the genetic output of a cell.
The research team has identified clusters of active genes that appear to act as ‘signatures’ of dormant myeloma cells. They are following up leads of ‘dormancy genes’ that are active in sleeping cells and so could be targeted with therapies — which could ‘force out’ and awaken dormant cells so they can be destroyed by chemotherapy.
In addition, the researchers are investigating how bone marrow biopsies could one day provide patients with a readout of their risk of relapse — which could make it possible to target therapies and treatment strategies to individual patients. Armed with knowledge that only cellular genomics can offer, the research team has — for the first time — a realistic shot at new cancer treatments, and even cures, based on eliminating or monitoring sleeping cancer cells in bone.
Hope Research: finding the ‘rogue clones’ at the root of autoimmune disease
Researchers at the Weizmann Institute and Garvan, led by Professor Chris Goodnow and Professor Ido Amit, are using cellular genomics to uncover ‘rogue clones’ of blood cells that give rise to many autoimmune diseases and blood cancers. They will identify vulnerabilities in these rogue clones to immunotherapy or other drugs, with the ultimate aim of eradicating them from the body.