Lifesaving ‘off-the-shelf’ cancer tracking immunotherapies underway

‘Off-the-shelf’ immunotherapies to fight aggressive forms of cancer, including relapsed ovarian and gastric cancers, are being developed in Clayton, Melbourne, thanks to almost $3 million in Federal Government funding awarded to lead participant Cartherics Pty Ltd.

Hudson Institute of Medical Research and Monash University researchers are partnering with industry leaders in cell therapies to develop the next generation of CAR-T cell immunotherapies for use in clinical trials, initially in patients with relapsed ovarian and gastric cancers.

The Melbourne team is the first globally to seek to develop these ‘off-the-shelf’ CAR-T cells using genetically engineered pluripotent stem cells from healthy donors.

Key points

• $2.987 million Federal Government grant supporting industry-academia collaboration
• Stem cells from healthy donors will be used to produce ‘off-the-shelf’ CAR-T cell cancer
immunotherapies.
• These next generation allogeneic (donor-derived) CAR-T cells could reduce the costs of
existing therapies by 90 per cent.
• Clinical trials for relapsed ovarian cancer and gastric cancer to start within three years.

As part of this unique industry-academia collaboration, Hudson Institute investigators Associate Professor Ron Firestein and Professor Graham Jenkin will harness their respective expertise in CRISPR genetic engineering and cell therapies to enable Cartherics to take the therapies to patients.

The $2.987 million Department of Industry, Innovation and Science Co-operative Research Centre project (CRC-P) grant has been awarded to Cartherics Pty Ltd, who are collaborating with Hudson Institute, Monash University, Mesoblast Ltd and Cell Therapies Pty Ltd to progress the research. A total of $12.6 million in funding and in-kind contributions is being injected into the project.

Hudson Institute Distinguished Scientist and CEO of Cartherics, Professor Alan Trounson, says the research aims to replicate the success of CAR-T cell immunotherapies seen in blood cancers such as leukaemia, in patients with solid tumours.

“Until now, CAR-T cell immunotherapies have involved taking stem cells out of a patient’s body, genetically ‘reprogramming’ them into cancer-fighting immune cells in the laboratory and putting them back into the patient’s body to track down and fight cancer,” Prof Trounson explains.

“However, seriously ill cancer patients are often immunocompromised, affecting the number and quality of their immune cells for fighting cancer. Growing their cells is time-consuming and can cost upward of USD$400,000 per patient – limiting access to these life-saving cancer therapies.

What are CAR-T cells?
Cancer immunotherapies strengthen the power of a patient’s immune system to fight cancer — as opposed to traditional cancer therapies, which use chemotherapy drugs and radiation to kill cancer cells.

CAR-T cells (chimeric antigen receptor technologies) are a form of cancer immunotherapies where scientists differentiate and genetically reprogram pluripotent stem cells into cancer fighting T-cells (a subset of white blood cells), which are put back into the body to fight cancer. Immunotherapies are emerging in the cancer research community as the ‘fifth pillar’ of cancer treatment alongside chemotherapy, radiation, surgery, and small molecules.

“CAR-T cell therapies are already showing incredible potential to treat a wide range of cancers with minimal use of chemotherapy and radiation. An off-the-shelf treatment has the potential to reduce the high costs of these immunotherapies by up to 90 per cent.”

The project will utilise donor stem cells with a rare and specific cell type – called triple HLA homozygous cells – from bone marrow registries and cord blood banks in Australia and the US.

“Having this cell type is almost like having an O Positive blood type – it’s compatible with almost half the Australian population, except it’s rare to find it in donors,” explains Associate Professor Ron Firestein, Head of Hudson Institute’s Centre for Cancer Research.

“Once we find these ‘rare’ compatible donor cells, they can be continuously regrown and stored – it’s a lifesaving, limitless resource. This renewable bank of pluripotent stem cells (iPSCs) can be gene edited and differentiated into cancer-fighting T cells.

“Like placing a GPS tracking device on these cells, we can instruct these T-cells to track down specific tumour types,” he says.

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