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.