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Walter and Eliza Hall Institute of Medicine (WEHI)

An innovative medical research institute that engages and enriches society
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CAR T-cell therapy is rapidly changing the way many blood cancers are treated, delivering hope for patients whose cancers have failed to respond or relapsed after more standard treatments. However, effective CAR T-cell therapies come with toxic, often life-threatening, side effects that prevent them from being used as first-line treatments. Furthermore, solid cancers with limited treatment options have yet to benefit from this clinical breakthrough.

What is the WEHI CAR T research?

WEHI and collaborators at the Weizmann Institute of Science in Israel are developing an approach to deliver safer and more effective CAR T-cell therapies by altering the molecular structures of the engineered cancer sensors that turn regular T cells into cancer-killing CAR T cells.

“Our vision is that this platform, which we call “programmed” CAR T-cells, or proCAR T-cells, would become a part of the development pipeline for a multitude of cancer immunotherapy products around the world, which would enable the selection of the best treatment for any one of the many types of cancer a patient may suffer.”

The team is testing their new technology in pre-clinical models of blood and brain cancers, with the goal of moving promising treatments rapidly into clinical trials. This effort will be aided by the recent establishment of the Centre of Excellence in Cellular Immunotherapy at the Peter MacCallum Cancer Centre (Peter Mac), a government-industry-nonprofit partnership that aims to fast-track clinical trials of innovative new Australian products, taking treatments from a basic research discovery in the lab to a treatment that will benefit patients as quickly as possible.

‘Changemaker‘ leadership

Matthew and Melissa Call are Harvard-trained molecular immunologists and structural biologists. Their research examines the functions of immune cells from the standpoint of what individual molecules do and how their shapes impact their functions. The duo have studied natural immune sensors, called receptors, for more than two decades and are now applying the insights they have gained to the exciting new field of immune cell engineering. Their research team includes protein engineers, biochemists, DNA experts and cancer biologists, and they collaborate with brain cancer experts and computational biophysicists to develop innovative solutions that ideally balance treatment efficacy and safety.

New & Novel Approach

CAR T cell therapy was deemed a remarkable medical breakthrough after it cured a case of pediatric leukemia in 2012. In the fast-moving world of cancer therapy innovation, CAR T therapy may not be considered particularly new by today’s standards. However, the WEHI-Weizmann approach is a clever innovation that brings a whole new dimension to CAR T therapy. By developing new molecular design tools, CAR T therapy can be optimised for both safety and efficacy in specific cancers. This means the patient can benefit from reduced side-effects while the therapy maintains its tumour killing ability. Initial tests are being conducted in blood and brain cancers, with the team hoping their work may bring hope to sufferers of glioblastoma, a particularly aggressive form of brain cancer with no effective treatments.

Scale

The genius behind the WEHI approach to receptor design, is that if successful, it can be incorporated into CAR T therapies across different cancer types and in treatment centres globally. CAR T-cell therapy is currently expensive but there is potential for costs to be brought down through improving the safety profile. Lower costs mean many more patients can benefit from CAR T therapy and its use can become more widespread.

Perhaps the most exciting aspect of scale is that the team have already received inquiries from researchers and clinicians in completely different areas of medicine and science, from treating Lupis and type 1 diabetes, to molecular counting applications in physics.

The WEHI team’s work has been so impressive that they attracted significant external funding, such that no further contribution was required from TDM. To see such leverage generated from our initial support is a dream come true for the TDM Foundation. We could not be more excited to see how this project continues to develop.

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