New 'immune brake' targeted for tumour control

Monday, 10 December, 2018

New 'immune brake' targeted for tumour control

Monash University researchers have shed new light on how some cancers are able to escape our immune system, in a breakthrough that has significant implications for the burgeoning field of immunotherapy — harnessing the power of our own immune system to seek out and destroy cancer.

The research was led by Dr Rich Berry, from the Monash Biomedicine Discovery Institute and ARC Centre of Excellence in Advanced Molecular Imaging, who explained, “The immune system is complex and highly regulated, comprising a number of accelerators and brakes. While the accelerators activate the immune system, the brakes are critical to maintain the balance and prevent the immune system attacking the body’s own healthy tissues.”

However, many tumours exploit this mechanism by expressing markers on their surface that engage the brakes, in order to restrict the immune system.

“One method of immunotherapy, termed ‘checkpoint inhibition’, involves blocking the immune brakes in order to unleash the formidable power of the immune system on the tumour,” Dr Berry said.

So far, two such brakes, PD-1 and CTLA-4, have been effectively targeted in the clinic. But despite some positive results, many patients do not respond to these treatments, so scientists are on the hunt for new immune brakes to target.

Using high-intensity X-rays at the Australian Synchrotron, the Monash team determined the 3D structure of a new immune brake, termed CD96. The structure reveals the precise molecular details of how CD96 binds to tumours.

“This is really exciting because studies using mouse models indicate that blocking CD96 might be even more effective at controlling tumour spread than the currently available treatments,” Dr Berry said.

Published in the journal Structure, the team’s studies could pave the way for future experiments aimed at further interrogating the role of CD96 in tumour control, and ultimately aid in the development of novel agents for the treatment of a range of cancers.

Image caption: Dr Rich Berry with lab members Dr Gabby Watson, Felix Deuss and Zhihui Fu. Image credit: Monash University.

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