Reducing the Side-Effects of Cancer Immunotherapy

Dr Jonathan Chee

Can inhibition of JAK-STAT signalling prevent autoimmunity and improve anti-tumour immunity?

Research Collaboration Award

$27,812.00

2023

The University of Western Australia, collaborating with University of Melbourne/St Vincent's Institute

Dr Jonathan Chee is a Research Fellow at the Centre for Respiratory Health, University of Western Australia. His team is at the forefront of testing novel therapies to improve immunotherapy efficacy in mesothelioma. Through this award and in collaboration with Professor Helen Thomas of St Vincent’s Institute in Melbourne, Dr Chee’s research aims to mitigate the side effects of cancer immunotherapytreatment, via initial pre-clinical testing in mouse models.

As the immune system triggers both anti-tumour and immunotherapy-induced side effects, it is important to develop strategies that will reverse side effects without compromising the anti-tumour immune response. Results showed that a clinically approved drug for treating rheumatoid arthritis successfully reversed autoimmune diabetes – a side effect of cancer immunotherapy – without impairing the immune system’s anti-tumour activity. This finding underscores the potential of this drug to manage immunotherapy side effects, and emphasises the critical role of drug scheduling in its clinical application.

Immune checkpoint therapies (ICT) which is a type of immunotherapy have revolutionised treatment of some advanced cancers, with durable responses in a subset of patients. Despite the clinical success, ICTs can cause a spectrum of toxicities known as immune-related adverse events.Symptoms range from mild, to severe to life-impeding. For example, development of type 1 diabetes after ICT is life-changing, requiring lifelong insulin therapy and glucose monitoring. As more patients undergo ICT, there is an urgent need for novel agents that effectively prevent these side effectswithout impeding the anti-tumour immune response.

Thanks to this award, Dr Chee and PhD student Ms Nicola Principe visited Prof Thomas' team in Melbourne. They shared expertise in immunogenetics and analysis techniques, while Prof Thomas' team provided training in laboratory techniques essential for type 1 diabetes research. Further, a researcher from Prof Thomas' team also visited Perth and presented their research to paediatric immunology and endocrinology specialists in WA at venues including the Perth Children's Hospital and Harry Perkins Institute of Medical Research.

This award also led to a publication in the Journal of Clinical and Translational Immunology as well as a successful US Department of Defense Career Development Award for Dr Chee.

Dr Chee explained, "This award facilitated a project that not only aims to enhance the quality of life for cancer patients by reducing therapy-related side effects but also provided a platform for learning from global leaders in this field.  A rare but severe side effect of cancer immunotherapy is diabetes, which occurs when the treatment designed to boost anti-tumour immunity inadvertently leads to the destruction of the patient’s insulin-producing cells. Professor Thomas recently identified a drug that counteracts this side effect in animals. Through our project, we determined the best timing to safely combine this drug with immunotherapy in animals with tumours, so that the anti-tumour effects of immunotherapy are maximised. This drug shows promise to alleviate side effects in cancer patients undergoing immunotherapy."