Dr Jonathan Worboys has been awarded a prestigious Wellcome Trust Career Development Award Fellowship to set up his lab at the Lydia Becker Institute of Immunology and Inflammation at The University of Manchester to research how nanoscale dimensions govern both the function and effective blockade of immune checkpoint receptors, such as TIGIT, which could lead to the design of more effective treatments for cancer patients.

Immune cells contain proteins on their surface that serve regulatory functions and are called ‘immune checkpoints’. These act to prevent catastrophic overactivation of immune responses. In diseases such as cancer, immune checkpoints can prevent effective immune responses and limit our ability to defend against tumours. Antibodies blocking immune checkpoint receptors can revive anti-tumour immunity and have revolutionised cancer therapies. Yet, effective responses remain infrequent, whilst severe immune-related side effects are frequent. The precise ways that immune checkpoints regulate immune responses are unknown and this prevents us from making more effective, safer drugs as well as being able to predict who will benefit from them.

Immune checkpoints organise into intricate nanoscopic patterns when they are functioning. This arrangement is critical to how they function, and Jonathan recently showed that this is true for an immune checkpoint called TIGIT. With this fellowship, Jonathan will build on his work to explore how the nanoscale organisation of such proteins is critical to their function. He recently discovered that nanoscale arrangements of such receptors are also observed upon effective blockade, and so his new lab at the Becker will try to understand this in more detail with the view to using this to design alternative drugs that work by preventing such proteins from forming into the arrangements they need to function properly.

Speaking about the award Jonathan said “This award not only allows me to start my own research group here but provides the flexibility, finances, and timeframe required to do ambitious and bold research. Immune checkpoints are extremely attractive therapeutic targets in oncology but have huge limitations. There are so many big unanswered questions, and my lab will aim to address some of these. I cannot wait to get going!”

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