It will help establish a gene therapy workforce to put Australia at the forefront of million-dollar product developments in the field of immunotherapy.
The trial, to be conducted by the new Li Ka Shing Cell and Gene Therapy Initiative, will be led by Professor John Rasko AO, an internationally recognised clinical haematologist and gene therapy expert.
The Li Ka Shing Cell and Gene Therapy Initiative is a collaboration between the University of Sydney, Centenary Institute, Royal Prince Alfred Hospital, Chris O’Brien Lifehouse, Sydney Catalyst, NHMRC Clinical Trials Centre, Sydney Cancer Research Network and Sydney Health Partners.
Pancreatic cancers are among the most aggressive cancers. Each year they affect over 3,000 men and women in Australia and some 500,000 worldwide, with a tiny seven percent long term survival rate. Despite accounting for only 2.4 percent of all diagnosed cancers, pancreatic cancer is disproportionately the fourth most common cause of cancer related deaths.
“Developing new treatments for rare cancers like pancreatic cancer is a major challenge,” Professor Rasko says. “Diagnosis of pancreatic cancer often occurs after the disease has spread and there are few clinical trials due to the relatively low patient numbers and the perceived lack of commercial return.”
Early immunotherapies focused on enhancing T-cell activity (white blood cells that kill cancer cells) and current drug immunotherapies act by ‘taking the brakes off’ the body’s immune system responses. But many clinical trials have seen large numbers of patients who fail to respond to these new immunotherapies.
“This ground breaking trial will be the first in Australia to test CAR T-cell immunotherapy in a solid tumour,” Professor Rasko says. “With support from the Li Ka Shing Foundation, we propose to expand capability by undertaking a potentially curative clinical trial.
“We believe our unique approach coupled with our experience in this field, provide compelling points of difference to other clinical trials taking place worldwide. With over 15 years’ experience, infrastructure development and refinements to our technique, we aim to break through years of minimal progress to accelerate treatment for pancreatic cancer.”
The Foundation was particularly impressed that this project will help build an Australian capability to deliver cutting-edge immunotherapies.
CAR T-cells are genetically reprogrammed white blood cells that target and kill a specific type of cancer. Chimeric antigen receptors (CARs), are engineered receptors added to a T-cell obtained from one’s own blood. These CARs target specific molecules found on the surface of cancer cells. The CAR T-cells are a living therapy derived from patients with cancer which are designed to attack their own cancer.
Blood is drawn from the patient and white blood cells called T-cells are separated and collected. At the Li Ka Shing Cell and Gene Therapy Initiative laboratories, the cells are genetically modified and reprogrammed to recognise specific cancer cells.
This is achieved by introducing a specific ‘chimeric antigen receptor’ – or CAR that targets specific markers on the surface of a cancer cells. The modified T-cells are then grown in a lab for about 10 days.
Chemotherapy is used to kill some of the patient’s white blood cells and help the body accept the new T-cells.
The reprogrammed T-cells are infused back into the patient where they multiply. They then ‘hunt’ cancer cells displaying the target protein, kill them, and proliferate to kill more cancer cells.
Developing new treatments for rare cancers like pancreatic cancer is a major challenge
Paul Tighe who is the Li Ka Shing Foundation’s Australian representative said the gift to the University of Sydney team continued the Foundation’s longstanding support for pioneering Australian research into gastro-intestinal cancers.
“Over many years the Li Ka Shing Foundation has supported Australia’s leading researchers in their vital work to help discover and research innovative cancer therapies. The Foundation was particularly impressed that this project will help build an Australian capability to deliver cutting-edge immunotherapies,” Mr Tighe said.
“This project also builds on the Foundation’s Endeavour Scholarships which helps to build stronger education links between Australia and Hong Kong by supporting 25 of Australia’s best and brightest students to study abroad each year and brings a similar number of overseas students to Australia.
“Our commitment to investing in Australia’s knowledge economy for the benefit of the entire community is some of the Foundation’s most important work and we are delighted to be partnering with the University of Sydney and Professor Rasko on this project,” Mr Tighe said.
The $4.5 million gift will provide the basis to build capacity in the cell and gene therapy workforce, specifically through training the next generation of scientific, clinical and regulatory personnel required to bring this new treatment alongside medicines, and medical devices for the benefit of patients.
“The current capacity to deliver cell and gene therapy clinical trials at Royal Prince Alfred Hospital is evident by many relevant trials already completed successfully, including an industry-sponsored pivotal study for CD19 CAR T-cells, said Professor Rasko.
“We are now at the critical point in time to capitalise on the excitement around the US FDA-approval of CAR T-cells, while creating significant new knowledge for the development of future products. We are in a position to provide local manufacturing of CAR T-cells for Australian patients and to deliver this service and to increase our clinical trial capacity via our international SAAC Consortium collaboration.
“Within one year of securing philanthropic support for this initiative, we anticipate to be providing the ongoing and necessary training for staff in specific manufacturing, and in the demanding clinical care of patients receiving potent immunotherapies. This model could also then be reproduced worldwide.
“It currently takes several months and costs in excess of $600,000 for a single treatment to be produced in the US and shipped to Australia. However, with support from the Li Ka Shing Foundation we can leverage existing infrastructure and expertise to replicate, refine and test an enhanced process through the proposed clinical trial.
“The net effect will be to implement a completely novel form of cancer therapeutic to increase local capacity and expertise while changing lives for the better.”
This visionary act of generosity from the Li Ka Shing Foundation unlocks the potential to create new-generation gene therapies that could offer new hope to cancer patients.
"The new Li Ka Shing Cell and Gene Therapy Initiative brings together some of the brightest minds across institutions working to transform health outcomes for cancer patients. It is a reminder that collaboration makes extraordinary things possible."