New EIC project to improve CAR T therapies in solid tumors

Partners in the international consortium CAR T-REX announce the awarding of a highly competitive EIC Pathfinder Open grant, following the positive evaluation of their project entitled ‘CAR T Cells Rewired to Prevent EXhaustion in the Tumour Microenvironment’. One of 57 projects selected amongst 858 submissions, with a total funding of €2.7M, CAR T-REX was recognised for its radical and ambitious vision to improve the efficacy and safety of CAR T-based solid tumour-targeted cell therapies.

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 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. In this regard, CAR T-REX aims to 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 TME) “switch off” the anti-tumoural immune response, potentially extending the utility and safety of current CAR T technologies.

György Vereb, Head of Chair at the Faculty of Medicine, University of Debrecen, adds: “For an ever-growing number of cancer patients, the current treatment options fail to provide a clear therapeutic benefit. Hence there is 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 to majorly contribute to the therapy of solid tumours.”

Rui A. Sousa, CEO of Stemmatters and 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, as well as Quality-by-Design methodologies and cGMP manufacturing, providing the right mix of skills needed to achieve the proposed goals. Stemmatters will ensure that processes are designed in compliance with harmonised quality standards and applicable regulatory requirements, as well as state-of-the-art methodologies, thus supporting a faster translation into the clinic setting”.

Overall, the CAR T-REX consortium expects to lay the foundation of an improved technology, with potential for significant scientific and societal impact, with recent estimations on the incidence and mortality for 25 major cancers across 40 European countries revealing 4 million new cases (excluding non-melanoma skin cancer) and 1.9 million cancer-related deaths in 2020.

About CAR T-REX

The consortium comprises three (3) academic and two (2) industrial partners from five (5) European countries. CAR T-REX is led by Stemmatters (Portugal), a regenerative medicine CDMO with expertise in the development and manufacturing of cell therapies under current Good Manufacturing Practice (cGMP). The company will adopt Quality-by-design (QbD) and risk assessment methodologies during product/process development, while levering its scientific and regulatory know-how to ensure a faster clinical translation of the CAR T cell therapy into the clinical setting. TargetGene Biotechnologies (Israel) brings expertise in new technologies for gene editing human cells. The company has developed a unique genome editing technology – T-GEE – which displays higher specificity and lower off-target events compared to the gold-standard CRISPR/Cas9, improving the safety of gene delivery systems. The Center for Research in Biological Chemistry and Molecular Materials (CiQUS) at Universidade de Santiago de Compostela (Spain) will employ its versatile delivery technology for non-toxic delivery of relevant cargos to immune cells, 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 Leibniz-Institut für Immuntherapie (Germany), provide expertise in immunology, CAR T cell design and development, as well as preclinical models of solid tumours - 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.

• By Centro Singular de Investigación en Química Biológica y Materiales Moleculares
• 22/06/2023
• CAR T cells