EIC awards €2.7M Pathfinder Open Grant to CAR T-REX Consortium to find better treatment for solid tumours
June 23, 2023
- CAR T-REX aims to:
- build novel auto-regulated genetic circuits controlled by microRNAs (miRNAs) in immune cells,
- employ a novel high-performance non-viral gene delivery platform for delivery of the synthetic miRNA constructs,
- select and benchmark the best-performing construct(s) in preclinical settings,
- execute GMP-like manufacturing run(s) for the final CAR T product.
The CAR T-REX Consortium brings together a multidisciplinary group of internationally recognised experts and companies across Europe. The project will start in June 2023 and run for four years.
Cell and gene therapies (CGT) are at the forefront of healthcare innovation, with the potential to transform the current therapy toolbox. Indeed, highly personalised (autologous) CAR T-cell therapies already have changed the treatment landscape dramatically, achieving partial remission, and 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 tumors has thus far failed to demonstrate clinical benefit; with antigen heterogeneity, limited infiltration into tumor tissue and in particular T-cell exhaustion/loss of function, negatively impacting clinical outcomes. In this regard, CAR T-REX aims to explore a novel paradigm for a new 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 tumors (and the immunosuppressive TME) ‘switch off’ the anti-tumoral immune response, potentially extending the utility and safety of current CAR T technologies.
György Vereb, Chair and Head of the Faculty of Medicine, University of Debrecen, adds: “For an increasing number of cancer patients, the current treatment options fail to provide a clear therapeutic benefit. This leaves an unmet clinical need which could be addressed by unleashing the curative potential of T cell-based therapies. It has therefore been an honour and an energizing—yet humbling—opportunity to be able to bring together this consortium which we expect will make a significant contribution to the therapy of solid tumors.”
Rui A. Sousa, CEO of Stemmatters & Coordinator, explains: “CAR T-REX brings together a multidisciplinary team with unique expertise and capabilities in genome editing, non-viral gene delivery, immunology and T-cell therapy. To this we can add Quality-by-Design (QbD) methodologies and Current Good Manufacturing Practices (cGMP), providing the right mix of skills needed to achieve the proposed goals. Stemmatters will ensure that processes are designed in compliance with harmonized quality standards and applicable regulatory requirements, as well as state-of-the-art methodologies, to support a faster translation into a clinical setting.”
Recent estimates of the incidence and mortality for 25 major cancers across 40 European countries reveal four million new cases (excluding non-melanoma skin cancer) and 1.9 million cancer-related deaths in 2020. The CAR T-REX Consortium expects to lay the foundation of an improved technology, with potential for significant scientific and societal impact.
About CAR T-REX
The consortium comprises three academic and two industrial partners from five European countries.
- CAR T-REX is led by Stemmatters (Portugal), a regenerative medicine contract development and manufacturing organisation (CDMO) with expertise in the development and manufacturing of cell therapies under cGMP. The company will adopt QbD and risk assessment methodologies during product/process development, while leveraging its scientific and regulatory know-how to ensure a faster translation of the CAR T-cell therapy into a clinical setting.
- TargetGene Biotechnologies (Israel) brings expertise in new technologies for gene editing human cells. The company has developed a unique genome-editing technology, known as T-GEE, which displays higher specificity and lower off-target events compared to the gold-standard CRISPR/Cas9. This will improve the safety of gene-delivery systems.
- The CiQUS at University of Santiago de Compostela (Spain) will employ its versatile delivery technology for the non-toxic delivery of relevant cargos to immune cells. This brings a high-value asset for industrial stakeholders working on the development of advanced therapies and nucleic acid-based therapeutics.
- The University of Debrecen (Hungary) and the Leibniz Institute for Immunotherapy (Germany) provide expertise in immunology, CAR T-cell design and development, as well as preclinical models of solid tumors—critical areas in a project focused on the development of a new CAR T technology.
This multidisciplinary collaboration brings together a unique set of researchers that encompass all the skills and resources needed to achieve the ambitious objectives of this project.
The European Innovation Council (EIC) was created as part of the EU Horizon Europe program. With a €10.1 billion budget, it aims to support game-changing ideas from early-stage research to proof of concept, technology transfer, and the financing and scaling-up of start-ups and SMEs. The EIC Pathfinder Open provides funding for projects in any field of science or technology based on high-risk/high-gain science-towards-technology breakthrough interdisciplinary research.