Scholar Spotlight: Professor Louis Chesler on the Future of Childhood Cancer Therapy

April 16, 2025

Professor Louis Chesler, an internationally recognised expert in paediatric oncology, is leading the charge to develop new, more effective treatments for childhood cancers that currently have poor outcomes.  

In this Scholar Q&A, Professor Chesler shares what drives his work, how his project, funded by the Oxford-Harrington Rare Disease Centre (OHC), is transforming immunotherapy for brain cancers, and what he hopes to achieve in the years ahead. 

What inspired you to focus your research on rare diseases, and how did you come to specialise in regulatable cell therapies? 

Louis Chesler: I have always wanted to work with children in an area of extreme need for them.  Childhood cancers are an area in which the ability to deliver benefit to children is complicated by the rarity of their diseases. While the challenges to the delivery of a new therapy are immense, the rewards that a success delivers are far greater.  

The concept that one could deliver a curative therapy to any child with an incurable cancer is an overwhelming and lifelong driver for most paediatric oncologists. 

L.C: I am attracted to the hypothesis that childhood cancers are developmental diseases - they form within developing tissues after oncogenic rewiring of proteins that are key regulators of development, molecular switches that govern tissue differentiation. Toggling these switches has the potential to restore normal development and differentiation and curatively eliminate cancer formation. 

This theory has been shown to work in practice in a small subset of childhood cancers, according to Professor Chesler. He now aims to develop a new set of drugs, which mimic the action of these molecular switches and offer the promise of more durable cures. 

Could you describe your awarded OHC Rare Disease Scholar project and its potential impact on patients with brain cancers? 

L.C: Our project focuses on equipping CAR-T cells — immune cells trained to seek and destroy cancer — with molecular “switches” that give us precise control over their activity. These switches, called iTags, allow us to turn the T-cell receptor on and off using drugs known as IMiDs, like lenalidomide and pomalidomide. 

T-cell therapies have been tremendously successful and are an exciting new form of immunotherapy for cancer. They have been most successful in leukaemias, but less so in brain and solid tumours, where they have difficulty surviving and expanding within the hostile environment of the tumours. 

L.C: The iTag molecular switches will allow us to "rest and recover" these cells and to more effectively target them in patients. We will use lenalidomide and pomalidomide (IMiDs drugs) to control T-cells in two upcoming trials of iTag CAR-T in patients.

The development of any new drugs for children with brain tumours in particular is an area of very high unmet need, where no new therapies have been introduced in about two decades.

How does the OHC’s model of combining funding with therapeutic development support help advance your work? 

L.C: Drug development in childhood cancers is financially challenging because there are thankfully very few patients. The only new therapies we have seen for children's cancers in the last twenty years have been designed to treat adult cancers and then repurposed or handed off to children to test. This is not always a successful approach given the unique biology of childhood tumours. 

A dedicated team and pathway that enables us to build drugs that specifically target childhood tumours is incredibly significant, particularly if the scheme can support the clinical development and licensing of the drug, which requires an enormous amount of resources.

What excites you most about your therapeutic approach, and how does it stand out as an innovation? 

L.C: Immunotherapies, including CAR-T therapies, have already delivered impressive survival benefits to children with cancer, but their efficacy for solid and brain tumours has been limited.

Our innovative molecular switching approach will enable very specific targeting of CAR-T to each tumour type, and we hope will increase the durability and power of these treatments. The iTag molecular switches and combination treatments with Imid drugs are readily translatable to clinical trials, and will enable us to move forward rapidly in further development of more effective immunotherapies.

What role do collaborations play in advancing your project?

L.C: For the first time, we as academic clinicians will possess most of the tools, resource and facilities needed to develop and rapidly deliver these treatments to patients, which represents a new paradigm for how we operate clinically. We have had very strong input from parents and patient representatives that this is an approach that they strongly support. 

How does the Rare Disease Scholar Award support your project? 
 
L.C: The Rare Disease Scholar awards have an impressive track record of identifying disease experts across the USA, Canada and now the UK, who aim to develop new drugs, and the internal expertise and industry experience of the Harrington Therapeutics Development Center (TDC) is a significant driver for applications. This funding will bring us into proximity with worldwide experts in the specialised technology we wish to apply to this project, and it will make available expert resources in all of the complicated facets of drug development in which we are not proficient as academic clinicians. It is a tremendously exciting scheme.    

About Professor Louis Chesler 

Professor Louis Chesler is working to discover and develop new drugs for children’s cancers that respond poorly to existing treatment. His research involves the three most common solid tumours of children – neuroblastoma, a nerve tumour, rhabdomyosarcoma, a muscle tumour, and medulloblastoma, a brain tumour. He leads the Paediatric Solid Tumour Biology and Therapeutics Group at The Institute of Cancer Research, London.