CAR T Cells Rewired to Prevent EXhaustion
in the Tumour Microenvironment

ABOUT 

CAR T-REX aims to improve efficacy, safety, scalability and cost of solid tumour cell therapies

​By combining innovative methods of genome editing and non-viral gene delivery, CAR T-REX will explore the engineering of transcriptional networks in CAR T-cells, to selectively circumvent T-cell exhaustion upon activation in the tumour microenvironment.

​Read more

OBJECTIVES

CAR T-REX aims to:

1. Build novel auto-regulated genetic circuits controlled by microRNAs (miRNAs) in immune cells.
2. Employ a novel high-performance non-viral gene delivery platform for delivery of the synthetic miRNA constructs.
3. Select and benchmark the best-performing construct(s) in preclinical settings.
4. Execute GMP-like manufacturing run(s) for the final CAR T product.

FOR PATIENTS

What are Cell and Gene Therapies?

Cell and gene therapies (CGT) are advanced medical approaches that involve manipulating cells or genetic material to treat various diseases and conditions. These therapies hold significant promise for the treatment of diseases that were previously considered difficult to treat or incurable. Highly personalised (autologous) CAR T-cell therapies have dramatically changed the treatment landscape, achieving partial or, in a significant number of cases, long-lasting full remission for patients with blood cancers. 

However, while CAR T-cell therapies have shown remarkable efficacy for the treatment of specific haematological malignancies, broad clinical use is limited by multiple factors, including high manufacturing costs and significant side effects. Moreover, treatment of patients with solid tumours has thus far failed to demonstrate clinical benefit, with antigen heterogeneity, limited infiltration into tumour tissue, and (especially) T-cell exhaustion/loss of function negatively impacting clinical outcomes.

CAR T-REX will explore a novel paradigm for the generation of improved CAR T cells. By combining non-viral gene delivery with precise genome editing of T cell autoregulatory pathways, CAR T-REX proposes a strategy to overcome the mechanisms by which solid tumours (and the immunosuppressive tumour microenvironment) “switch off” the anti-tumoural immune response, potentially extending the utility and safety of current CAR T technologies.

CAR T-REX consortium expects to lay the foundation of an improved technology, with potential for significant scientific and societal impact.

Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union. Neither the European Union nor the granting authority can be held responsible for them.

Follow CAR T-REX on Social Media