Novel technologies for tracking and engineering of CAR T cells

Chimeric antigen receptor (CAR) T cell therapy has emerged as a groundbreaking approach in cancer treatment, particularly for haematological malignancies. However, its broader application to solid tumours has been limited, partly due to rigorous and expensive manufacturing processes that often drive T cells into a terminally differentiated state, reducing their in vivo proliferation and persistence.
This thesis presents novel technologies to address these limitations, focusing on both the engineering and tracking of CAR T cells. The research includes the development of high-avidity antigen-multimers, experimentally validated for their ability to specifically detect CAR T cells using flow cytometry and microscopy. These multimers were optimised and tested on various CAR constructs, demonstrating their potential for monitoring CAR T cell fitness and persistence in patient samples. Additionally, the thesis explores the development of dextran-based nanoparticles for gene delivery. These nanoparticles were tested in vitro for their efficiency in targeted gene delivery to T cell lines and primary human T cells, resulting in effective gene expression with minimal cytotoxicity.
These findings offer insights and practical solutions for enhancing the development and manufacturing processes of CAR T cell therapies, paving the way for more cost-effective treatments targeting both haematological malignancies and solid tumours.