Chimeric antigen receptor (CAR) T-cell therapy: Engineering immune cells to treat liver diseases
Elmar Jaeckel, Scott L. Friedman, Michael Hudecek, Ulrike Protzer
Abstract
Endogenous T cells recognise antigens through human leukocyte antigen (HLA)/peptide complexes. However, HLA polymorphism poses a major challenge to the development of broadly applicable adoptive T-cell therapies. Engineered T cells can circumvent this barrier by targeting surface antigens independently from HLA through a synthetic chimeric antigen receptor (CAR) with an antibody-derived recognition domain fused to intracellular signalling motifs. CAR T-cell therapies have transformed the treatment of B-cell malignancies in haematology, and recent studies demonstrate therapeutic potential against solid tumours. In this review, we provide an overview of the fundamental principles and key achievements of CAR technology, with a focus on its applications in hepatic viral infections, autoimmune liver diseases, and hepatobiliary tumours. We also highlight emerging senolytic therapies targeting senescent cells and hepatic fibrosis, as well as regulatory CAR T cells designed to induce liver-specific immune tolerance in transplantation. Finally, we discuss ongoing and future research aimed at improving the specificity, efficacy, and safety of CAR-based therapies as "living drugs" for targeted, durable, and personalised treatment of liver diseases.