Targeting new therapeutics in transplantation

Tuesday, 25 May 2021

Your team is investigating an immunological target to improve stem cell transplantation and to treat GVHD. What can you tell us about the research to date?

This is a new project and collaboration between me and Professor Christian Engwerda, who leads the Immunology and Infection Laboratory and is Head of the Infectious Diseases program at QIMR Berghofer. I am very interested in the pathways and mechanisms that drive inflammation, as these are important targets in diseases such as GVHD and autoimmunity. Current clinical approaches rely on broad immunosuppressive regimens to control disease, which have considerable off-target effects on beneficial immunity. Here we have an opportunity to explore a novel, more targeted approach to control inflammation and tissue damage in allo-SCT, whilst retaining other protective elements of immune function.

What have you previously discovered in this area?

We have recently identified interferon lambda (IFNλ) as an important driver of intestinal stem cell-driven gastrointestinal repair during allo-SCT. This is very exciting, as damage to the gut during pre-transplant conditioning is a key driver of the inflammatory cascade that leads to GVHD. We have shown that peri-transplant treatment with pegylated IFNλ significantly improves gut-barrier integrity and graft-versus-host disease survival in preclinical models of allo-SCT. This finding is readily translatable as clinical grade IFNλ is available and its safety profile has been established in other settings.

What are the main research challenges?

The biological processes that underpin both graft-versus-host disease and graft-versus-leukaemia effects are very similar, so finding new treatments for allo-SCT complications can be extremely difficult. However, there is a lot of terrific research in this area particularly on the inflammatory processes that initiate disease, so there is a lot of potential for new treatment approaches.

How long before your work might impact on patient care?

Over the next two years this project will validate a novel immunological  target in allo-SCT, specifically focussing on GVHD and immune reconstitution studies in pre-clinical models. This study will also fund the development of new therapeutic reagents targeting this inflammatory pathway, that will also be tested in preclinical models. If we are successful, we will then move to clinical grade reagent development as well as safety and efficacy trials. This process is likely to be over 5 years, although the urgent need to new treatments in this area often enables more rapid translation.

This project has attracted interest and investment from CSL. How will that help shape and accelerate the research?

The investment and support from CSL is critical to the project and we are very excited to be collaborating with them on this study. CSL has a strong interest in developing new therapeutics in the transplantation arena and are currently investing in this area of research. By partnering with CSL on this project we gain the benefit of their extensive drug development experience and access to resources that will enhance the study and guide translation.

What’s your Holy Grail – the one thing you’d like to achieve in your research career?

In the context of allo-transplantation where patient outcomes are often poor, the clear goal is to improve survival and quality of life for these cancer patients. My research is focussed on understanding the mechanisms that drive disease, and aims to identify novel targets for disease prevention/treatment, as well as develop new tools for diagnostics to enable early intervention. I would be thrilled to know that my work led to a significant improvement in patient outcomes in some way.

Who has inspired you in work or life?

I have been inspired by a series of terrific mentors who are not only highly successful in their fields, but also understand the importance of having fun while you do it. The nature of research is that there is a lot of unsuccessful attempts to achieve something, whether that be experimental, publishing or funding, and it can be difficult to stay optimistic at times. So, they have taught me to enjoy the process and celebrate the wins where possible, as persistence is the key to long term success.

How do you achieve work-life balance?

Like everyone else, work-life balance is an ongoing challenge for me – particularly at the moment as I have two very young boys (2yrs & 6mo). Whilst I often feel like I am running from one end of the see-saw to the other, having a good team is critical on many levels. I am very lucky to have a small, but reliable group of terrific researchers, as well as great collaborators who are generous with their time and resources.

There’s an app for that. What’s new on your phone?

Not exactly new, but definitely my most used app would be Audible – the best way to get a few books in when life is crazy and quiet time is hard to come by!


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