Scientists from the Garvan Institute of Medical Research are playing pivotal roles in two major new cancer research collaborations funded by NHMRC Synergy Grants, announced by Mark Butler, the Minister for Health and Aged Care. These ambitious five-year programs bring together leading scientists across multiple Australian institutes to tackle two of the most pressing problems in cancer – extending the benefits of immunotherapy to solid tumours and preventing lethal metastases.
By bringing together diverse expertise and the latest technologies, the programs are set to improve our understanding of cancer biology, and importantly, to translate these scientific advancements into better therapies for patients.
Improving immunotherapy for prostate cancer
Garvan’s Professor Paul Timpson is a key researcher on a project to unlock the potential of CAR T cell therapies for prostate cancer to be spearheaded by Professor Gail Risbridger from Monash University’s Biomedicine Discovery Institute. CAR T cell immunotherapy involves scientists genetically engineering a patient’s T cells to recognise and attack their cancer. While CAR T cell therapies have led to remarkable outcomes in certain blood cancers, they have not yet proven effective against solid tumours.
The team aims to methodically analyse why CAR T cells struggle to infiltrate and persist within solid tumour environments of prostate cancer. Professor Timpson will lead the application of new intravital imaging techniques via Garvan’s ACRF INCITe Centre to visually track CAR T cells within tumours.
“We can effectively map the cellular roadblocks inside solid tumours using these advanced microscopy approaches,” Professor Timpson said.
After determining why CAR T cells fail in solid cancers, the team plan to then engineer smarter CAR T cells to steer around those obstacles to improve outcome for this form of therapy.
“This consortium can fill knowledge gaps that have long stood in the way of successful solid cancer CAR T therapy. Our approaches could potentially make these next-generation therapies accessible for many major solid malignancies beyond prostate cancer,” Professor Timpson said.
The research team’s other key members are Professor Phillip Darcy from Peter MacCallum Cancer Centre, Associate Professor Renea Taylor and Associate Professor Daniela Loessner from Monash University’s Biomedicine Discovery Institute and Professor Ian Davis from Monash University’s Eastern Health Clinical School.
Blocking the growth of lethal metastases
Associate Professor Marina Pajic brings pancreatic cancer expertise as a key researcher on a Synergy Grant team tackling the critical problem of lethal cancer metastases by identifying vulnerable targets in the tumour environment. The project will be steered by Associate Professor Delphine Merino from the Olivia Newton-John Cancer Research Institute and the La Trobe University School of Cancer Medicine. Metastasis, the ability of cancer cells to spread to new sites, is responsible for 90% of cancer deaths.
The team will use cutting-edge technologies to provide new insights into how aggressive metastatic cancer cells emerge and interact with their surrounding tissue environments in breast, gastrointestinal and pancreatic cancer.
The goal is to pinpoint why some cancer cells can successfully spread to other organs and how the local environment supports this, then to use these insights to develop new combination therapies to eliminate metastases.
Their techniques will include single-cell sequencing to examine the genetic material of individual cancer cells, cellular barcoding to uniquely label and track them, and spatial omics to map the locations of specific proteins and RNA molecules within patient tumour samples and mouse models.
“By studying both the cancer cells and the supportive tissues they invade through at higher resolution than ever before, we aim to find new vulnerabilities we can target to prevent or treat metastatic disease,” said Associate Professor Pajic.
“Metastasis is a complex process involving both evolving cancer cells and receptive tissue environments. It has been extremely difficult to study and target due to its dynamic, interconnected nature. Our cross-institutional team offers the diversity of disciplines and skillsets needed to assess the phenomenon from multiple angles – to find commonalities and differences across cancer types that will lead to key therapeutic targets,” she said.
The research team’s other key members are Professor Michael Samuel from the Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia; Professor Matthias Ernst and Professor Yi-Ping Phoebe Chen from the Olivia Newton-John Cancer Research Institute/La Trobe University; and Dr Shalin Naik from The Walter and Eliza Hall Institute of Medicine.
Professor Paul Timpson is a Conjoint Professor at St Vincent's Clinical School, UNSW Medicine & Health. Associate Professor Marina Pajic is a Conjoint Associate Professor at St Vincent's Clinical School, UNSW Medicine & Health.