Visualising the unexpected in DIPG « Charlie Teo Foundation

Visualising the unexpected in DIPG

Researcher name: Dr Anne Rios
Institution: Princess Máxima Centre for Paediatric Oncology, Netherlands
Grant Name: Research Rebels
Grant amount (AUD): $200k
Grant Awarded: 2024
Status: Ongoing

Meet the Researcher

Dr Anne Rios is a tenured Group Leader of the Dream 3D Lab and Head of the Imaging Centre at the Princess Máxima Centre for Paediatric Oncology in the Netherlands.

Anne spent five years in Australia completing her senior post-doctoral fellowship at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne. During her time in Australia, Anne won the prize for most creative young scientist at Sydney University’s Centenary Institute Medical Innovation Awards.

Anne is also a pioneer of high-resolution whole organ imaging and was the first to image the development of the mammary gland. Her research provided important biological insights for Breast Cancer and was published in the most prestigious biomedical journal, Nature.

Anne was an Expert member for the European Union’s Marie-Curie fellowships, and winner of the L’Oréal-UNESCO Woman in Science Award in 2021. She is the founder of the Art Foundation, The SuperNatural, using immersive art to tell the story of science.

DIPG is a deadly paediatric brain cancer located in a critical area of the brain, making surgical removal challenging and radiotherapy minimally effective. Despite global efforts to develop new treatments, survival rates have stagnated for decades. Recently, therapies using chimeric antigen receptor (CAR) T cells have shown promise, reducing symptoms and tumour size in DIPG patients, but the benefits are not long-lasting. To enhance the effectiveness of these therapies, A/Prof. Anne Rios’ project aims to use artificial intelligence, genomics, advanced 3D imaging technology, and a novel patient representative DIPG 3D organoid model for experimental testing to improve the overall efficacy of CAR T cell therapy.

This project is game-changing because it combines novel DIPG organoids that strongly resemble patient tumours, artificial intelligence, and 3D imaging technology to analyse the behaviour of individual functional cells in a way that hasn’t been done before. This innovative approach could provide crucial insights into how cellular immunotherapies work and how we can further exploit them towards improving therapy design for DIPG patients.

This project could potentially help patients with DIPG by enhancing the effectiveness and durability of T cell therapies. The use of DIPG organoids to model the function of these immunotherapies can provide clinicians and scientists with better indications on how these therapies will perform in patients and the changes we need to make.

DIPG is a lethal paediatric brain cancer with limited treatment options due to its critical location in the brain and tumour complexity. Recent efforts have focused on developing CAR T cell therapies, which have shown initial success but lack long-term efficacy. To improve this, the Rios Lab have developed a new human DIPG organoid model to study DIPG and test long-term CAR T cell treatments. Through applying BEHAV3D on this model, a comprehensive imaging platform to profile T Cells at single cell resolution, the Rios lab have revealed a potent cytotoxic T cell cluster, termed ‘super-engager’ T cells, which show promise for enhanced DIPG targeting. However, balancing therapeutic effectiveness, safety, and long-term responses requires further testing. This project aims to enhance control over the input cells delivered to patients and introduce an innovative strategy for producing superior engineered T cell products.

The overarching aims of this grant includes:

Aim 1. Implementing a selection strategy to enrich for the potent super-engager GD2 CAR T cell phenotype.
Aim 2. Leveraging the BEHAV3D comprehensive imaging platform to dynamically profile the most promising selected T cell products and confirm their super-engager behavioural profile.