[en] Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable success in treating haematologic malignancies. However, the rise in clinical use has highlighted substantial challenges related to T cell- and tumour-intrinsic mechanisms. Additionally, the tumour microenvironment can render these treatments dysfunctional. Extensive attempts in the field are optimizing the key elements of CAR T cell products for therapy, including antigen specificity and affinity, metabolic fitness, phenotypic stability and manufacturing. Recent efforts in transcriptomic and epigenetic profiling, as well as high-throughput functional screening methods, have identified new classes of targets, binders and mechanisms to be exploited. Advances in gene editing and delivery offer opportunities to translate those strategies into clinical trials. Here we discuss the multifaceted exploration of CAR T cell engineering approaches and emerging directions, highlighting the available strategies that can be built on to create the next generation of cellular therapies.
Disciplines :
Biotechnology
Author, co-author :
Nguyen, Thi Tham ; Université de Liège - ULiège > Département des sciences cliniques > Hématologie
Ho, Patrick ; Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany
Staudt, Sarah; Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany
GREGOIRE, Céline ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'hématologie clinique ; Cell Therapy & Immuno-Engineering Program, Center for ImmunoTherapy and Precision Immuno-Oncology, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA
Ziegler-Martin, Kai; Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany
Hudecek, Michael ; Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany ; National Center for Tumor Therapy (NCT WERA), Würzburg, Germany ; Bavarian Cancer Research Center (BZKF), Würzburg, Germany ; Außenstelle Zelluläre Immuntherapie, Fraunhofer Institut für Zelltherapie und Immunologie (IZI), Würzburg, Germany
Melenhorst, J Joseph ; Cell Therapy & Immuno-Engineering Program, Center for ImmunoTherapy and Precision Immuno-Oncology, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA
Caers, Jo ; Université de Liège - ULiège > Département des sciences cliniques > Hématologie
Luu, Maik ; Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany. Luu_m@ukw.de ; National Center for Tumor Therapy (NCT WERA), Würzburg, Germany. Luu_m@ukw.de ; Bavarian Cancer Research Center (BZKF), Würzburg, Germany. Luu_m@ukw.de ; Außenstelle Zelluläre Immuntherapie, Fraunhofer Institut für Zelltherapie und Immunologie (IZI), Würzburg, Germany. Luu_m@ukw.de
Language :
English
Title :
Fine tuning towards the next generation of engineered T cells.
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